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Archive for the ‘Cardiac Stem Cells’ Category

Analysis on Worldwide Autologous Stem Cell Based Therapies Market Inclinations Exhibit Growing Demand During The Period Until 2025 – Wheel Chronicle

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Analysis on Worldwide Autologous Stem Cell Based Therapies Market Inclinations Exhibit Growing Demand During The Period Until 2025 - Wheel Chronicle

Drug Treats Inflammation Related to Genetic Heart Disease – Technology Networks

When young athletes experiences sudden cardiac death as they run down the playing field, it's usually due to arrhythmogenic cardiomyopathy (ACM), an inherited heart disease. Now, Johns Hopkins researchers have shed new light on the role of the immune system in the progression of ACM and, in the process, discovered a new drug that might help prevent ACM disease symptoms and progression to heart failure in some patients.

"We realized that heart muscle inflammation in ACM is much more complicated than we thought, but also might provide a therapeutic strategy," saysStephen Chelko, Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and senior author of the new paper, inSept. inCirculation.

In ACM, patients often harbor mutations in any of the five genes that make up the cardiac desmosome -- the gluelike material that holds heart cells together and helps coordinate mechanical and electrical synchronization of heart cells. Because of this, it's often called "a disease of the cardiac desmosome." In patients with ACM, heart cells pull apart over time, and these cells are replaced with damaged and inflamed scar tissue. These scars can increase risk of instances of irregular heart rhythms and lead to sudden cardiac death if the scar tissue causes the heart wall to stiffen and renders it unable to pump.

If a person is aware they carry an ACM-causing genetic mutation, doctors help them avoid cardiac death through lifestyle changes, such as exercise restriction, and medications that keep their heart rate low. However, there are currently no drugs that treat the underlying structural defects of the desmosome. People who live for many years with ACM still accumulate scar tissue and inflammation in their hearts, leading to chronic heart disease.

"We tended in the past to view ACM as something that kills due to a sudden arrhythmic event," said Chelko. "But now we're starting to also see it as a chronic inflammatory disease that can progress more slowly over time, leading to heart failure."

Chelko and his colleagues wanted to determine the molecular cause of inflammation in the hearts of people with ACM. So they studied mice with an ACM-causing mutation, as well as heart muscle cells generated from stem cells isolated from an ACM patient. They found that the inflammation associated with the disease arose from two separate causes. First, they noticed high levels of macrophages, a type of immune cell that's normally found at sites of inflammation, such as around cuts or scrapes that are healing.

"Macrophages are usually the good guys who help heal a wound and then leave," said Chelko. "But in ACM they're permanently setting up shop in the heart, which, over time, reduces its function."

Chelko's team also found that in ACM, the heart cells themselves are triggered by a protein known as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) to produce chemicals called cytokines, which act as homing beacons for other inflammatory cells and molecules. When the researchers treated mice or isolated cells with a drug blocking NF-B, heart cells stopped producing many of these cytokines, leading to decreased inflammation and infiltration of inflammatory cells. In mouse models of ACM, animals treated with the NF-B-blocking drug Bay-11-7082 had a twofold increase in heart function, measured by how much blood their hearts could pump over time compared with untreated ACM animals. They also had a twofold reduction of damaged and inflammatory scar tissue in the heart.

More than one-third of patients with ACM who die of sudden cardiac death have no previous cardiac symptoms, so wouldn't ever know to seek treatment. However, for relatives of these people who discover that they carry a genetic mutation causing ACM -- or those who discover the mutation for other reasons -- a drug could help stave off long-term heart disease, Chelko said.

While the Bay-11-7082 drug is currently only used in the lab for experimental purposes, the U.S. Food and Drug Administration has approved canakinumab, a drug that targets the same inflammatory pathway, for use in juvenile arthritis and a collection of rare auto-inflammatory syndromes. Canakinumab is also being studied for use in coronary artery disease. Chelko's group is now investigating whether this drug would have the same effect as Bay-11-7082 in ACM.

"We're very excited to have found an FDA-approved drug that can reduce heart inflammation in ACM, and we're eager to do more research to ultimately help those who carry these genetic mutations," said Chelko.

Reference:Chelko, et al. (2019) Therapeutic Modulation of the Immune Response in Arrhythmogenic Cardiomyopathy. Circulation. DOI:https://doi.org/10.1161/CIRCULATIONAHA.119.040676

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Drug Treats Inflammation Related to Genetic Heart Disease - Technology Networks

Research Roundup: Genomic Dark Matter Mutation and More – BioSpace

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Mutation Found in Dark Matter of the Genome New Target for Cancer

The so-called dark matter of the genome is the non-coding regions that make up about 98% of the genome. Researchers at the Ontario Institute for Cancer Research (OICR) recently identified a novel cancer-driven mutation in this region that is linked to brain, liver and blood cancer. They published the two studies in the journal Nature.

Non-coding DNA, which makes up 98% of the genome, is notoriously difficult to study and is often overlooked since it does not code for proteins, said Lincoln Stein, co-lead of the two research studies and Head of Adaptive Oncology at OICR. By carefully analyzing these regions, we have discovered a change in one letter of the DNA code that can drive multiple types of cancer. In turn, weve found a new cancer mechanism that we can target to tackle the disease.

The mutation is dubbed U1-snRNA, and it appears to disrupt normal RNA splicing, which changes the transcription of genes that drive cancer. The mutation was identified in tumors of patients with specific subtypes of brain cancer and was found in almost all of the samples. The cancer was sonic hedgehog medulloblastoma. It was also found in samples of chronic lymphocytic leukemia (CLL) and hepatocellular carcinoma.

Our unexpected discovery uncovered an entirely new way to target these cancers that are tremendously difficult to treat and have high mortality rates, said Michael Taylor, pediatric neurosurgeon and senior scientist in Development and Stem Cell Biology and Garron Family Chair in in Childhood Cancer Research at The Hospital for Sick Children and co-lead of the studies. Weve found that with one typo in the DNA code, the resultant cancers have hundreds of mutant proteins that we might be able to target using currently available immunotherapies.

Diagnosing Lyme Disease in 15 Minutes

About 300,000 people are diagnosed with Lyme disease each year. Borrelia burgdorferi is transmitted by the bite of infected Ixodes ticks, and if untreated, can cause neurologic, cardiac, and rheumatologic complications. Current testing involves two complex tests, ELISA and western blot. Researchers have developed a rapid microfluidic test that can provide comparable results in as little as 15 minutes. It will require more refinement and testing before widespread use.

Gene Therapy for Wet Age-Related Macular Degeneration Shows Promise

Research was recently presented on six patients who received a gene therapy for wet age-related macular degeneration (AMD). The patients have gone at least six months without continued injections for the disease that were previously required every four to six weeks. The therapy, which is injected into the eye, generates a molecule much like aflibercept, a broadly used anti-VEGF drug.

How Dementia Spreads Throughout Brain Networks

Frontotemporal dementia (FDT) is similar to Alzheimers disease, but tends to hit patients earlier and affects different parts of the brain. Researchers studied how well neural network maps made from brain scans in healthy people could predict the spread of brain atrophy in FTD patients over several years. They recruited 42 patients at the UCSF Memory and Aging Center with a form of FTD and 30 with another form. They received MRI scans and then follow-up scans a year later to determine how the disease had progressed. They found that the standardized connectivity maps were able to predict the spread of the disease.

Mucus and Microbes: A Therapeutic Gold Mine.

A specific type of molecule called glycans that are found in mucus prevent bacteria from communicating with each other. Mucus also prevents the bacteria from forming infectious biofilms. It is also pointed out that more than 200 square meters of our bodies are lined with mucus. There are hundreds of different types of glycans found in mucus, and most of them are responsible for suppressing bacteria. Katharina Ribbeck, a professor at the Massachusetts Institute of Technology, says, What we have in mucus is a therapeutic gold mine.

Mechanisms that Regulate Brain Inflammation

The role of brain inflammation in diseases like Alzheimers and Parkinsons is becoming better understood. Researchers recently identified mechanisms that regulate brain inflammation, which has the potential to open new avenues for treating and preventing these diseases. The scientists found that a protein called TET2 modulates the immune response in microglia, immune cells in the brain, during inflammation. In mice engineered not to have TET2 in the microglia, neuroinflammation is reduced. Normally, TET2 with other proteins regulates the activity of genes by removing specific chemical markers from DNA, but TET2 appears to behave differently in microglia.

Pilot Study: Even Short-Term Vaping Causes Lung Inflammation

Research out of The Ohio State University Comprehensive Cancer Center found cellular inflammation was caused by e-cigarette, i.e., vaping, use in both long-term smokers and people who did not smoke. They used bronchoscopy to evaluate for inflammation and smoking-related effects and found a measurable increase in inflammation after only four weeks of vaping without nicotine or flavors. The amount of inflammation was small compared to the control group, but the data suggests that even short-term use can result in inflammatory changes at a cellular level. Inflammation in smoking is a driver of lung cancer and other respiratory diseases.

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Research Roundup: Genomic Dark Matter Mutation and More - BioSpace

SIDS May Be Linked To A Genetic Inability To Digest Milk, Study Finds – Moms

Sudden Infant Death Syndrome (SIDS), sometimes known as crib death, occurs when an infant under the age of one dies inexplicably.The typically healthy child will often die while sleeping and is the leading cause of death of children between the ages of one month and one year, claiming approximately 3000 lives a year. There has been little known about the cause of SIDS but new research is now showing that some form of SIDS could be linked to a genetic inability to digest milk.

A study out of theUniversity of Washington School of Medicine focused on the "mitochondrial tri-functional protein deficiency, a potentially fatal cardiac metabolic disorder caused by a genetic mutation in the gene HADHA."

It found that newborns with had the genetic mutation are unable toproperly digest some of the fats found in breastmilk, resulting in cardiac arrest. It found that "the heart cells of affected infants do not convert fats into nutrients properly," and once these fats build up they can cause serious heart and heart health issues.

There are multiple causes for sudden infant death syndrome, said Hannele Ruohola-Baker, who is also associate director of the UW Medicine Institute for Stem Cell and Regenerative Medicine. There are some causes which are environmental. But what were studying here is really a genetic cause of SIDS. In this particular case, it involves a defect in the enzyme that breaks down fat.

Lead author on the study Dr. Jason Miklassaid that it was his experience researching heart disease that prompted him to look at the possible link with SIDS. There was one particular study that had noted a link between children who had problems processing fats and who also had cardiac disease that caused him to delve a little deeper.

Miklas andRuohola-Baker teamed up to begin their own research study.If a child has a mutation, depending on the mutation the first few months of life can be very scary as the child may die suddenly,Miklas noted. An autopsy wouldnt necessarily pick up why the child passed but we think it might be due to the infants heart-stopping to beat.

Were no longer just trying to treat the symptoms of the disease, Miklas added. Were trying to find ways to treat the root problem. Its very gratifying to see that we can make real progress in the lab toward interventions that could one day make their way to the clinic.

Ruohola-Baker says their findings are a big breakthrough in understanding SIDS. There is no cure for this, she said. But there is now hope because weve found a new aspect of this disease that will innovate generations of novel small molecules and designed proteins, which might help these patients in the future.

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SIDS May Be Linked To A Genetic Inability To Digest Milk, Study Finds - Moms

Merck Receives Positive EU CHMP Opinion for Two New Regimens of KEYTRUDA (pembrolizumab) as First-Line Treatment for Metastatic or Unresectable…

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of two regimens of KEYTRUDA, Mercks anti-PD-1 therapy, for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC). KEYTRUDA, as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is recommended in patients whose tumors express PD-L1 (combined positive score [CPS] 1). This recommendation is based on data from the pivotal Phase 3 KEYNOTE-048 trial, in which KEYTRUDA, as monotherapy and in combination with chemotherapy, demonstrated a significant improvement in overall survival, compared with standard treatment (cetuximab with carboplatin or cisplatin plus 5-FU), in these patient populations.

Head and neck cancer remains a devastating disease with poor long-term outcomes and advances in survival have been difficult to achieve for more than 10 years said Dr. Jonathan Cheng, vice president, clinical research, Merck Research Laboratories. The positive EU CHMP opinion further validates the potential of KEYTRUDA, as monotherapy and in combination with chemotherapy, to help patients and address the high unmet need in this aggressive form of head and neck cancer.

Merck currently has the largest immuno-oncology clinical development program in HNSCC and is continuing to advance multiple registration-enabling studies investigating KEYTRUDA as monotherapy and in combination with other cancer treatmentsincluding, KEYNOTE-412 and KEYNOTE-689. The CHMPs recommendation will now be reviewed by the European Commission for marketing authorization in the EU, and a final decision is expected in the fourth quarter of 2019.

About Head and Neck CancerHead and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. Most head and neck cancers are squamous cell carcinomas that begin in the flat, squamous cells that make up the thin surface layer of the structures in the head and neck. Two substances that greatly increase the risk of developing head and neck cancer are tobacco and alcohol. It is estimated that there were more than 705,000 new cases of head and neck cancer diagnosed and over 358,000 deaths from the disease worldwide in 2018. In Europe, it is estimated that there were more than 146,000 newly diagnosed cases of head and neck cancer and around 66,000 deaths from the disease in 2018.

About KEYTRUDA (pembrolizumab) InjectionKEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,000 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

About KEYTRUDA (pembrolizumab) InjectionKEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,000 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) IndicationsMelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung CancerKEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung CancerKEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck CancerKEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial CarcinomaKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [CPS 10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Microsatellite Instability-High (MSI-H) CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric CancerKEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal CancerKEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical CancerKEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular CarcinomaKEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell CarcinomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell CarcinomaKEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated PneumonitisKEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grade 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated ColitisKEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination with Axitinib)Immune-Mediated HepatitisKEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination with AxitinibKEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated EndocrinopathiesKEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%), receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal DysfunctionKEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin ReactionsImmune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse ReactionsImmune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including cHL, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related ReactionsKEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple MyelomaIn trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal ToxicityBased on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse ReactionsIn KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with HCC were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent of which (1%) included hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%). The most common adverse reactions (>1%) resulting in permanent discontinuation of KEYTRUDA, axitinib or the combination were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). When KEYTRUDA was used in combination with axitinib, the most common adverse reactions (20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

LactationBecause of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Pediatric UseThere is limited experience in pediatric patients. In a trial, 40 pediatric patients (16 children aged 2 years to younger than 12 years and 24 adolescents aged 12 years to 18 years) with various cancers, including unapproved usages, were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients received KEYTRUDA for a median of 3 doses (range 117 doses), with 34 patients (85%) receiving 2 doses or more. The safety profile in these pediatric patients was similar to that seen in adults; adverse reactions that occurred at a higher rate (15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), increased transaminases (28%), and hyponatremia (18%).

Mercks Focus on CancerOur goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit http://www.merck.com/clinicaltrials.

About MerckFor more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the worlds most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimers disease and infectious diseases including HIV and Ebola. For more information, visit http://www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USAThis news release of Merck & Co., Inc., Kenilworth, N.J., USA (the company) includes forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the companys management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the companys ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the companys patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the companys 2018 Annual Report on Form 10-K and the companys other filings with the Securities and Exchange Commission (SEC) available at the SECs Internet site (www.sec.gov).

Please see Prescribing Information for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf andMedication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

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Merck Receives Positive EU CHMP Opinion for Two New Regimens of KEYTRUDA (pembrolizumab) as First-Line Treatment for Metastatic or Unresectable...

6 Bodily Tissues That Can Be Regenerated Through Nutrition – The Epoch Times

Spontaneous recovery from disease is often painted as superstition but our body can heal itself

It may come as a surprise to some, especially those with conventional medical training, but the default state of the body is one of ceaselessregeneration. Without the flame-like process of continual cell turnover within the bodylife and death ceaselessly intertwinedthe miracle of the human body would not exist

In times of illness, however, regenerative processes are overcome by degenerative ones. This is where medicine may perform its most noble feat, nudging the body back into balance with foods, herbs, nutrients, and healing energies and intentions.

Today, however, drug-based medicine invariably uses chemicals that lackregenerative potential; to the contrary, they commonly interfere with bodily self-renewal in order to suppress the symptoms against which they are applied.

In other words, most medicines attack disease symptoms rather than support the bodys own ability to combat disease.

Over the course of the past few years of trolling MEDLINE (the National Institutes of Healths website produced by the National Library of Medicine), we have collected a series of remarkable studies on a topic considered all but heretical by the conventional medical systemspontaneous remission.

There is actually a broad range of natural compounds with proven nerve-regenerative effects. A 2010 study published in the journalRejuvenation Research, for instance, found a combination of blueberry, green tea and carnosine have neuritogenic (i.e. promoting neuronal regeneration) and stem-cell regenerative effects in an animal model ofneurodegenerative disease.Other researched neuritogenic substances include:

There is another class of nerve-healing substances, known asremyelinatingcompounds, which stimulate the repair of the protective sheath around the axon of the neurons known as myelin. Myelin is often damaged in neurological injury and/or dysfunction, especially autoimmune and vaccine-induceddemyelination disorders.

It should also be noted that evenmusicandfalling in lovehave been studied for possibly stimulating neurogenesis, regeneration and/or repair of neurons, indicating that regenerative medicine does not necessarily require the ingestion of anything; rather, a wide range oftherapeutic actionsmay be employed to improve health and well-being, as well.

[To view the first-hand biomedical citations on these neuritogenic substances, visit GreenMedinfosneuritogenicresearch page online.]

Glycyrrhizin, a compound found within licorice that is also a powerfulanti-SARS virus agent, has also been found to stimulate the regeneration of liver mass and function in the animal model of hepatectomy. Other liver regenerative substances include:

[To view the first-hand biomedical citations, visit GreenMedinfosliver regenerationresearch page on the topic online.]

The medical community has yet to harness the diabetes-reversing potential of natural compounds. Whereas expensive stem cell therapies, islet cell transplants, and an array of synthetic drugs in the developmental pipeline are the focus of billions of dollars of research, annually, our kitchen cupboards and backyards may already contain the long sought-after cure for type 1 diabetes. Nature has a way of providing the things our bodies need.

The following compounds have been demonstrated experimentally to regenerate the insulin-producing beta cells, which are destroyed in insulin-dependent diabetes, and once restored, may (at least in theory) restore the health of the patient to the point where they no longer require insulin replacement.

[To view the first-hand biomedical citations onbeta cell regeneration, visit GreenMedinfos research page on the topic online.]

Secretagogues are substances in the body that cause other substances to be secreted, like sulfonylureas, which triggers insulinrelease. Secretagogues, includingsynthetic secretagogues, can increase the endocrine glands ability to secrete more of a hormone. But even better are substances thattruly regeneratehormones which have degraded. They do this by emitting electrons into potentially carcinogenic transient hormone metabolites. One of these substances isvitamin C.

A powerful electron donor, this vitamin has the ability to contribute electrons to resurrect the form and function of estradiol (estrogen; E2), progesterone, and testosterone, for instance. In tandem withfoods that are able to support the function of glandslikethe ovaries, vitamin C may represent an excellent complement or alternative to hormone replacement therapy.

Not too long ago, it was believed that cardiac tissue was uniquely incapable of being regenerated. A new and rapidly growing body of experimental research now indicates that this is simply untrue. A class of heart-tissue regenerating compounds, known asneocardiogenicsubstances, are able to stimulate the formation of cardiac progenitor cells which can differentiate into healthy heart tissue. Neocardiogenicsubstances include the following:

Another remarkable example of cardiac cell regeneration is through what is known as the fetomaternal trafficking of stem cells through the placenta. The amazing process known as fetal microchimerism allows a fetus to contribute stem cells to the mother which are capable of regenerating her damaged heart cells, and possibly a wide range of other cell types.

Curcuminandresveratrolhave been shown to improve recovery from spinal cord injury. Over a dozen other natural compounds hold promise in this area, which can be viewed on GreenMedinfosspinal cord injurypage online. As far as degenerative joint disease, i.e. osteoarthritis, there are a broad range of potentially regenerative substances, with 50 listed on the sitesosteoarthritisresearch page.

Regenerative medicine poses a unique challenge to the current medical paradigm, which is based on costly drug trials, patents, and an economic infrastructure supported by drug-based interventions. It is a simple truth that symptom suppression is profitable. It guarantees both the perpetuation of the original underlying disease and the generation of an ever-expanding array of additional, treatment-induced symptoms known as side effects.

But cures, especially those that come from natural sources, dont have this built-in income potential. Worse perhaps, from a Big Pharma perspective, they can not be easily patented. In the current regulatory environment, that means that companies have no incentive to conduct the costly trials required to have these cures approved by the FDA and then used in clinical settings. Without patents, they cant be controlled and sold.

But suppressing symptoms with drugs that cause side effects requiring other drugs is a non-sustainable, infinite growth model. It is doomed to fail and eventually collapse.

The current approach also interferes with the bodys natural regenerative and immune capabilities. Cultivating diets, lifestyles and attitudes conducive to bodily regeneration can interrupt this pathological circuit. With true health, we can attain the bodily freedom that is a precondition for the liberation of the human spirit.

SayerJiis the founder ofGreenmedinfo.com, a reviewer at theInternational Journal of Human Nutrition and Functional Medicine, co-founder and CEO ofSystome Biomed, vice chairman of the board of theNational Health Federation, and steering committee member of theGlobal GMO Free Coalition.This article was originally published on GreenMedinfo.com

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6 Bodily Tissues That Can Be Regenerated Through Nutrition - The Epoch Times

First Patient Enrolled in Novel Stem Cell Trial for Heart Failure Treatment – Newswise

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Newswise Washington, D.C., October 1, 2019 MedStar Heart & Vascular Institute has enrolled its first patient to a clinical trial to determine whether cardiac stem cells reduce inflammation enough to improve heart function in patients with heart failure severe enough to require a left ventricular assist device, or LVAD. STEMVAD is a randomized, double-blinded, placebo-controlled study that will assess the effects of multiple intravenous administration of CardioCells proprietary mesenchymal stem cells (MSCs). It is expected to enroll 30 patients.

The STEMVAD trial is the next step in MedStar Heart & Vascular Institutes earlier research that discovered one of the major problems in heart failure is persistent inflammation," said Stephen Epstein, MD, director of Translational and Vascular Biology Research at MedStar Heart & Vascular Institute. "And these mesenchymal stem cells control inflammation, leading to improved heart function.

Approximately six and a half million adult Americans have heart failure, of whom 200,000 to 250,000 are estimated to have end-stage heart failure and need a heart transplant. However, with the very low supply of donor hearts, LVADs are increasingly used. An LVAD is a small pump that helps circulate the patients blood when their heart becomes too weak to pump effectively on its own. Although highly effective in alleviating symptoms and improving longevity, patients with LVAD support have a high incidence of serious complications.

Innovative therapies to improve heart function and outcomes of patients with advanced heart failure are sorely needed, added Selma Mohammed, MD, PhD, research director of the Advanced Heart Failure Research Program at MedStar Heart & Vascular Institute.

If we are successful in showing intravenously delivered stem cells improve outcomes in patients, the results would likely extend to the general population of heart failure patients, and in the process, fundamentally transform current paradigms for treating heart failure, concluded Ron Waksman, MD, director of Cardiovascular Research and Advanced Education at MedStar Heart & Vascular Institute. For more information on whether patients may qualify for the trial, call Michelle Deville, research coordinator, at 202-877-2713 or email michelle.deville@medstar.net.

###

Conflict of Interest Statement: Dr. Stephen Epstein is an equity holder in CardioCell, serves on its Board, and consults for the company.

About MedStar Heart & Vascular Institute:MedStar Heart & Vascular Institute is a national leader in the research, diagnosis and treatment of cardiovascular disease. A network of 10 hospitals and 170 cardiovascular physicians throughout Maryland, Northern Virginia and the Greater Washington, D.C., region, MedStar Heart & Vascular Institute also offers a clinical and research alliance with Cleveland Clinic Heart & Vascular Institute, the nations No. 1 heart program. Together, they have forged a relationship of shared expertise to enhance quality, improve safety and increase access to advanced services. MedStar Heart & Vascular Institute was founded at MedStar Washington Hospital Center, home to the Nancy and Harold Zirkin Heart & Vascular Hospital. Opened in July 2016, the hospital ushered in a new era of coordinated, centralized specialty care for patients with even the most complex heart and vascular diagnoses.

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First Patient Enrolled in Novel Stem Cell Trial for Heart Failure Treatment - Newswise

Regenerative medicine today: Are diabetes and vascular disease treatments ready for the clinic? – Science Magazine

Regenerative medicinewhich involves regrowing damaged or dysfunctional cells, tissues, and organs, in order to treat and cure human diseaseholds great promise. Discoveries in stem cell research and tissue engineering as well as advances in regulatory and industry support have brought regenerative medicine treatments closer than ever to the clinic. Two areas showing particular potential are diabetes and vascular disease. Whether acquired or congenital, diabetes afflicts millions of people worldwide and presents a tremendous burden both in terms of physical deterioration and loss of economic capacity. Current treatments rely mainly on lifetime injections of exogenous hormones and palliative treatments with pharmaceuticals, neither of which can address the lack of properly functioning beta cells in the pancreas. Similarly, vascular diseases are among the leading causes of mortality and morbidity. The ability to generate new, clinical-grade vascular tissue is critical to the long-term treatment of complications arising from ischemic injury, stroke, aneurisms, retinopathy, and other acute and chronic vascular conditions; significant progress has been made in using stem cell sources to produce this tissue. But what is needed to get such potentially transformative treatments over the finish line?

During this webinar, the speakers will:

This webinar will last for approximately 60 minutes.

University of Miami Miller School of MedicineMiami, FL

Juan Domnguez-Bendala, Ph.D., is director of the Stem Cell Development for Translational Research and research associate professor of surgery at the Diabetes Research Institute (DRI), University of Miami Miller School of Medicine. Before joining the DRI faculty, he worked at the Roslin Institute (Scotland, United Kingdom) under the supervision of one of the creators of Dolly the sheep. He obtained his Ph.D. there and acquired considerable experience in embryonic stem cell research and state-of-the-art genetic engineering techniques. Working with other DRI faculty and international collaborators, Dr. Domnguez-Bendala is currently involved in several projects that focus on the use of stem cells to obtain pancreatic islets that could be safely and efficiently transplanted into patients with type 1 diabetes. He is also working on new methods for the endogenous regeneration of pancreatic beta cells.

Mayo ClinicRochester, MN

As deputy director of Translation for the Center for Regenerative Medicine, medical director of the Advanced Product Incubator, and director of the Van Cleve Cardiac Regenerative Medicine Program at the Mayo Clinic in Rochester, Minnesota, Dr. Behfar has worked to establish off-the-shelf good manufacturing practice (GMP)-grade regenerative technologies. Over the last two decades, his program has engaged in evaluating cell-based technologies for restoration of skeletal and cardiac muscle function. During this time, he initiated clinical trials in heart failure along with Dr. Andre Terzic, using stem cells to restore cardiac function and treating over 400 patients. Through that experience, it was discovered that exosome secretion was the primary driver of the regenerative action of stem cells. More specifically, an exosome product was purified (termed purified exosome product, or PEP) from our regenerative platform that revealed massive biopotency in activating regeneration through mitogenic, antioxidant, anti-inflammatory and provasculogenic influence. This discovery now serves as the basis for many preclinical and clinical efforts at Mayo Clinic.

Science/AAASWashington, D.C.

Dr. Oberst did her undergraduate training at the University of Maryland, College Park, and her Ph.D. in Tumor Biology at Georgetown University, Washington D.C. She combined her interests in science and writing by pursuing an M.A. in Journalism from the Philip Merrill College of Journalism at the University of Maryland, College Park. Dr. Oberst joined Science/AAAS in 2016 as the Assistant Editor for Custom Publishing. Before then she worked at Nature magazine, the Howard Hughes Medical Institute, The Endocrine Society, and the National Institutes of Mental Health.

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Regenerative medicine today: Are diabetes and vascular disease treatments ready for the clinic? - Science Magazine

Technological Growth of Autologous Stem Cell Based Therapies Market (2019-2025) | Business Overview, Product Specification and Top Manufactures &…

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Technological Growth of Autologous Stem Cell Based Therapies Market (2019-2025) | Business Overview, Product Specification and Top Manufactures &...

SWIFT: Uzel and Skylar-Scott are Paving the Way for the Future of Bioprinting – 3DPrint.com

A few weeks ago, Mark Skylar-Scott and SbastienUzel,researchers working in Jennifer Lewis Lab at Harvards Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS), came up with a breakthrough new technique that could one day provide organ tissues for therapeutic use. The method, called SWIFT (sacrificial writing into functional tissue), allows 3D printing to focus on creating the vessels necessary to support a living tissue construct.

All organs need blood vessels to supply their cells with nutrients, but most lab-grown organoids lack a supportive vasculature. This is where the SWIFT method comes into play, 3D printing vascular channels into living tissues. Two weeks ago, 3DPrint.com went into some of the main details of the research, but now we have gone straight to the source and spoken with two of the co-first authors of the paper, which came out on September 6 in Science Advances, to understand the process behind the method, as well as the collaborative work shaping the future of Harvards bioengineering aspirations.

Inspired by the 3D bioprinting techniques emerging from the Lewis lab and the community in general, Mark [Skylar-Scott] and I decided that is was time to tackle, head-on, the challenge of cell function and density, and tissue volume, which were keeping us from reaching organ manufacturing at therapeutic scale, revealed Uzel. Using patient-derived organoids or 3D cell spheroids as our building blocks appeared like a natural choice. They are cellularly dense and exhibit great functional and architectural similarities with the organs they are meant to mimic.

A branching network of channels of red, gelatin-based ink is 3D printed into a living cardiac tissue construct composed of millions of cells (yellow) using a thin nozzle to mimic organ vasculature.

Uzel went on to explain that the idea of this SWIFT printing process really took shape when we speculated that once jammed into a dense slurry, those organoids would behave as predicted by the science of colloid suspensions and therefore could serve as a supporting living matrix for the free form templating of perfusable vessels. The rest was many months of testing and optimization!

Both researchers and their colleagues found a way to pack living cells tightly enough together to replicate the density of the human body. Actually, they assembled hundreds of thousands of organ building blocks (OBBs) composed of patient-specific-induced pluripotent stem cell-derived organoids, which offer a pathway to achieving tissues with the requisite cellular density, microarchitecture, and function required. At the same time, they introduced vascular tunnels via embedded 3D bioprinting in between the OBBs to mimic blood vessels that are needed to deliver fluids, like nutrients and oxygen, that are vital to survival.

As an example, the group of researchers created a perfusable cardiac tissue that fuses and beats synchronously over a seven-day period. The SWIFT biomanufacturing method enables the rapid assembly of perfusable patient and organ-specific tissues at therapeutic scales. What is so novel about the new lab-grown heart tissue is that it beats, just like a normal human heart, and has an embedded network of the blood vessels that would be needed to survive if it was ever transplanted into a patient. It still needs to be tested before it can be used in humans, and their channels arent yet truly blood vessels, but if the innovation works for heart tissue, the experts expect SWIFT could also be used for other organs.

Living embryoid bodies surround a hollow vascular channel printed using the SWIFT method.

We believe that this new technique addresses the technical roadblocks of cell density and manufacturing scalability. From a biology standpoint, making each building block more functional and performant, meaning being able to contract stronger in the context of cardiac tissues, for instance, is among the challenges that need to be overcome and will require gaining even more insights in pluripotent cell differentiation and how it can be recapitulated in vitro. We will also need to better emulate the multicellular and hierarchical complexity of the vessels as found in the human body, proposed Uzel.

The researchers consider that on the manufacturing side of the process, the cost of reagents for scaling up cell culture and differentiation will have to be drastically reduced for de novo organ manufacturing to be a viable option looking into the long term.

When it comes to considering SWIFT as one of the main advances in the last few years towards bioprinting organs, Skylar-Scott claims it would be presumptuous to say that SWIFT came out of a vacuum.

There have been many great works in this decade that have applied 3D printing to generate perfusable tissues, and our work builds on these efforts. What really does get us excited about SWIFT is how we have brought the matrix for embedded printing to life, and, by using organoids, we hope that SWIFT may serve as a bridge between the bottom-up self-assembly of developmental biology, and the top-down directed assembly of 3D printing, Skylar-Scott asserted. We can say, with reasonable certainty, that any successful engineering of a complex organ from scratch will require a combination of these two approaches.

The recent progress in the field of bioprinting has brought us a lot closer to the eventuality of 3D printed organs. The field is moving faster than we expected. Just five years ago, we were afraid to use the big O word [organs], but we are now, as a field, beginning to tentatively see a path forward, he continued.

SWIFT is one of the projects at Harvard that could ultimately be used therapeutically to repair and replace human organs with lab-grown versions containing patients own cells. There is actually so much research at Wyss and SEAS, from scaling up tissue engineering to engineering miniature kidneys, its even one of the first places where researchers entirely 3D-printed an organ-on-a-chip with integrated sensing. Moreover, the creation of highly-organized multicellular biological tissues and organoids is structurally diverse and complex, so tissue manufacturing techniques require extreme precision, making us wonder what type of bioprinter the researchers are using.

According to Skylar-Scott, they exclusively use custom made printers and extruders in the lab, that for the purposes of wacky experimentation, they offer the most versatility by far. He also suggests that these printers are large and expensive, but, for many processes, including SWIFT, were confident that it can be replicated with commercially available or open-source alternatives.

As part of the SWIFT project evolution, collaborations are underway with Wyss Institute faculty members Christopher Chen, Professor of Biomedical Engineering and director of the Tissue Microfabrication Laboratory at Boston University and Sangeeta Bhatia, Professor at MITs Institute for Medical Engineering & Science (IMES) and Electrical Engineering & Computer Science (EECS), to implant these organ-specific tissues created by SWIFT into animal models and explore their host integration, as part of the 3D Organ Engineering Initiative, co-led by 3D printing pioneer and Wyss core faculty member, Jennifer Lewis, and Chen.

We are currently working on rodent models for our initial in vivo phase. Along with perfecting our technique and improving the performance of printed tissues, we are investigating how small vascularized SWIFT-printed cardiac constructs integrate within the animal and connect to the existing blood stream. Once confident that the SWIFT tissues behave appropriately in small animals, the hope is to move to larger chunks of tissue to be tested on larger animals, in preparation for tests in humans in the long run, revealed Uzel.

The collaborative work to make SWIFT a reality is a great example of integrating various disciplines and professionals into bioprinting projects.

A process like SWIFT combines various expertise, from developmental biology to materials science or mechanical engineering. The strength of the lab is that it is built around great talents in all those disciplines. The Lewis lab is roughly divided into bioprinting and non-bioprinting work, but the two groups share technologies, techniques, and printing inks very frequently, said Scott.

Tissues created without SWIFT-printed channels display cell death (red) in their cores after 12 hours of culture (left), while tissues with channels (right) have healthy cells.

He went on to explain that it is unlikely that 3D printing can print all length-scales of an organ from centimeter-scale ventricles to micrometer scale capillaries. So, we specifically designed the SWIFT process so that it can work with organoids being built by the stem cell and developmental biology communities. By bridging the 3D printing and organoid fields, we believe there is a great potential for collaboration, and have already heard from researchers interested in using SWIFT to test scaling up their organoid systems. This interest has come from all sorts of specialists in different organs, including kidney, liver, heart, and brain.

With so much going on, a typical day at the lab for Uzel and Skylar-Scott is not so typical. Although most of the daily tasks involve a combination of cell culture, printing ink formulation and characterization, CAD design and fabrication of printing and perfusion systems, tissue maintenance, imaging, and analysis. At busy times, Skylar-Scott says they could have upwards of four hours of work per day just to keep their cells fed, which has led to many long nights and weekends in the lab.

Similar to most academic labs, graduate students and postdocs all have two or three projects running in parallel.

For SWIFT, we had to culture so many cells for a single print, that we were only running about one print per week. Since staring at cells doesnt make them grow faster, it is often helpful to have a second project to focus on, joked Skylar-Scott.

For example, they are currently working on new 3D printer hardware technology and focused on testing the SWIFT printed tissues in vivo so they can begin to test for additional function. All in a days work.

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SWIFT: Uzel and Skylar-Scott are Paving the Way for the Future of Bioprinting - 3DPrint.com

Moving beyond hype: Could one-two treatment restore damaged heart muscle? – University of Wisconsin-Madison

Heart attacks can cause immediate death. But in survivors, the blockage of blood flow can kill so many heart muscle cells that heart failure can follow months or years afterwards. Heart disease is the leading cause of hospital admission and death in the United States.

A heart attack causes a loss of muscle and leaves the heart with a scar that does not contract and so impairs the hearts pumping function, says Tim Kamp, a professor of medicine who is co-leader of a new grant designed to attack two roadblocks that have stymied efforts to restore heart muscle with muscle cells grown from stem cells.

Kamp, who directs the Stem Cell and Regenerative Medicine Center at the University of WisconsinMadison, says, Everybody involved in treating these patients knows that this scarring often leads to a continual decline in heart function with heart failure and even death.

The UWMadison researchers used approved surgical devices to locate the damaged heart muscle, and then injected the supportive matrix and committed cardiac muscle cells. The circle outlines target zone established before surgery; black dots show the sites that were injected in this mouse study. Amish Raval, work performed at UWMadison in collaboration with Biologics Delivery Systems.

Sixteen percent of men, and 22 percent of women, develop heart failure after myocardial infarction heart attack. Coronary artery disease the category that includes stoppage of blood flow causes one in seven deaths in the United States.

Adult stem cell injections seemed a logical way to form new heart muscle cells and repair the damaged muscle. But in dozens of experiments, the cells either washed out of the heart or failed to develop into the specialized muscle cells the cardiomyocytes that power cardiac contractions. The benefits were mixed, modest at best, says Kamp.

After years of preliminary investigations, however, Kamp and Amish Raval, a professor of cardiology, researcher and entrepreneur, hope that a combination of two cutting-edge approaches would use a fabric-like material to prevent wash-out and successfully implant cardiomyocytes to damaged hearts.

Aided by a Regenerative Medicine Innovation Project grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, the two will lead a group to test that idea in pigs over two years.

Having committed cells could be a major advance, Raval says. The first stem-cells therapies started with cells that I call the model T. Now, we are moving to the Buick. The cells originate as induced pluripotent stem cells (iPSCs) a relative of embryonic stem cells that is based on reprogramming adult cells.

Two Madison-based businesses, and sources at the University of WisconsinMadison, also helped to fund the research. Fujifilm Cellular Dynamics Inc., one of the largest commercial sources of stem cell products, produces the committed cardiac progenitor cells that will be tested. These committed cells are ready to transform themselves into cardiomyocytes.

Fujifilm bought CDI, a company whose founders included Kamp and UWMadison stem cell pioneer James Thomson, but the operations remain in Madison. Kamp has no ownership position but is a consultant for the company.

Raval is a founder and board chair of the second commercial supporter, Cellular Logistics, Inc., which makes a freeze-dried matrix from the same proteins that naturally holds cardiomyocytes in place in the heart. The material is called extracellular matrix (ECM) because it scaffolds cells from the outside.

When the heart pumps, internal pressures often eject would-be replacement cells through lymph channels and blood vessels. Ravals group has already shown in mice that injecting extracellular matrix proteins along with new cells creates mechanical restraints that avoid the wash-out problem.

The extra-cellular matrix to be used in the NIH grant at UWMadison helped retain stem cells (yellow dots) in a pig heart. When similar cells (blue) were injected without the matrix, the cells spilled out of the heart muscle through the needle track and lymph channels.Eric Schmuck and Amish Raval, work performed at UWMadison. Eric Schmuck and Amish Raval, work performed at UWMadison

The injected scaffold may have another advantage for regenerating muscle after heart attack, Kamp notes. The ECM replenishes the scarred area to become more hospitable to the replacement cardiomyocytes. The effect may be based on chemical and mechanical signaling between the ECM and the regenerating cells.

Pigs hearts are quite close to human hearts in size and structure. The grant will cover tests on four groups of 12 pigs each following myocardial infarction:

If the combination is effective, Raval adds, We plan to proceed toward a Food and Drug Administration application for an investigational new drug, which would allow us to begin human trials.

With the passion and concern of a working cardiac surgeon, Raval says those trials would focus on patients who have not been helped by the best medical management we know today and they are not candidates for heart transplant or mechanical assist devices. The only other option is palliative or hospice care.

As Raval notes, More people are surviving heart attacks, and thats great. But many are left with a scar in the heart muscle a dead zone. That scar can enlarge, and the damage can spread. So we are seeing an increasing number of patients with heart failure. Thats why we are moving forward with this project.

This research is being funded by NIH grant 1U01HL148690-01.

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Moving beyond hype: Could one-two treatment restore damaged heart muscle? - University of Wisconsin-Madison

How growing mini human hearts is advancing precision medicine, drug discovery – The Sociable

Instead of testing drugs on patients directly,a cutting-edge precision medicine process is creating miniature beating hearts as primary test subjects.

Be sure to check outPart I,Part II, and Part IIIof our interview series on precision medicine!

Imagine a doctor recommends a strong medicine to a patient, a medicine that often causes cardiac problems in patients.

However, instead of testing the drug on the patient, the doctor gets a lab-grown, mini-sized replica of the patients heart.

The drugs are administered on the mini heart until the right drug is found. Only then is it administered to the patient.

Imagine a situation where you take cells from a particular patient, make these little mini hearts for that patient, and test potential therapies in the in vitro system before you subject the patient to those therapies

Before you start thinking Chromosome 6, (a reference to a Robin Cook book) see what Kevin Costa, Co-Founder and Chief Scientific Officer at Novoheart told The Sociable.

Their MyHeart platforms miniature hearts made from human tissue could be bringing in a revolution in precision medicine as well as drug discovery.

Precision medicine isnt just human-based, its individual based, and you can get increasingly precise, he says.

With a mini heart pumping away like any regular one, one can start to specialize a little bit more. For example, finding out the specifics of a disease in different ethnic backgrounds, like the Jewish population, African-American, Caucasian, or Asian.

So you can go from just having a human heart to an Asian, Caucasian, African, or whatever you want. You can also look at differences between male and female. So thats starting to get a little more precise, he explains.

So we can really get to the level of precision of an individual.

You can even make these tissues from an individual patient. Literally, weve got hearts in our laboratory that were made from a particular patients skin cells, he gushes.

Novoheart focuses on stem cell and tissue engineering for next-generation drug development and discovery. They are primarily a service company providing screening services based on their human tissue engineering technology, which they call the MyHeart platform.

Read more: Deep tech, big data, and their impact on precision medicine

The MyHeart platform consists of several different cardiac assays of human cardiomyocytes, human heart cells that are derived from human induced pluripotent stem (IPS) cells, which means human stem cells that can be differentiated into any cell type of the body.

The IPS cells are then mixed with the cardiomyocytes to make a 3D Structure and then cast into different types of tissues or layers of cells that Novoheart uses to measure electrophysiology or strips of tissue to measure contractility.

Rather than subjecting the patient to testing various cocktails of drugs, if we could get some information early on about whether a particular patient is more susceptible to a therapy, we can treat at a very granular, precise level for each patient

So its kind of like the electrical and mechanical side of how the heart works. We make these little mini hearts that pump like human hearts and give us measurements that clinicians are interested in, for example, cardiac output stroke volume he says.

Everything that Novoheart does is based on human cells. Tissue engineering has evolved to use human cells instead of rodent, and this was the basis for the original idea for Novoheart.

The company combined Costas expertise in tissue engineering in cardiac mechanics, Co-founder and CEO Ronald Lis expertise in human stem cells and cardiac electrophysiology, and Co-founder and Scientific Advisory Board member, Michelle Khines expertise in microfluidic platforms.

Drug discovery currently involves a process that starts with investigating a few thousand compounds in the laboratory, from which a couple of hundred that look promising can be impressed in an animal model.

Then you have to sort of take a leap of faith in moving from testing on animals to human patients. Thats the next step in the clinical trial process, Costa explains.

Costa says for every drug that enters a clinical trial process, 90% of them fail. Maybe, one out of ten that goes back out of several hundred is actually a go, after which clinicians consider candidates and try to get FDA approval.

Its a very inefficient and time-consuming process involving a couple of billion US dollars. Typically, to go from initial concept to approval, it can take over a decade, he says.

The Novoheart team thinks that part of the inefficiency lies in that leap of faith in going from animals to patients.

The way to help improve that process would be if we could get information in a human based heart system before actually testing on patients.

Novoheart has found a less risky way in terms of safety concerns for trying things on patients for the first time.

Also, if a compound doesnt work, you can reiterate in the laboratory and improve its safety and efficacy before moving on to clinical trials. This could ensure an increase in the success rate of clinical trials from 10% to who knows 50% or more.

According to Costa, one of the top reasons that drugs fail in the regulatory approval process is because of cardiac side effects, which is a major roadblock. That is a part of the reason Novoheart focuses on cardiac miniatures.

We focus on cardiac because thats our expertise. But the drugs that we are testing can be for any body part or disease because they all have to go through at least a cardiac safety assessment, he says.

They make two classes of heart tissue, a healthy heart tissue as well as diseased ones.

These organoids are designed thinking ahead towards that day when we will be able to have a little heart organoid, a liver organoid and a little brain organoid, all communicating with one another, kind of like a little humanoid

If you want to find a drug thats going to cure diabetes, you want to ensure it isnt going to give you heart disease in the process. So you can try it on the healthy heart tissue and see if its safe. If it causes arrhythmias or hypertrophy, it would be a problem for the patient, he says.

The other kind of tissue they make is diseased tissue.

If youre trying to develop a drug to cure heart disease, you need to have a model of that disease. So Novoheart is actively involved in that as well, he says.

Will they branch out then to other organoids? How about the liver?

Read more: Machine learning will be able to predict diseases years before onset of symptoms

Costa says Novoheart is thinking about combining different types of organoids together with the technology theyve developed. Costa paints a little picture of the future,

These organoids are designed thinking ahead towards that day when we will be able to have a little heart organoid, a liver organoid and a little brain organoid, all communicating with one another, kind of like a little humanoid.

Currently, its not particularly cost-effective to be able to do this for every single patient. However, Costa says, as the process becomes more streamlined and economical, the future is hopeful.

Imagine a situation where you take cells from a particular patient, make these little mini hearts for that patient, and test potential therapies in the in vitro system before you subject the patient to those therapies, he says.

Precision medicine isnt just human-based, its individual based, and you can get increasingly precise

This will have a major impact on medicine because, often, a cardiologist has to consider multiple therapies for a patient. In the current way of doing things, they try out and see what works on the patient. If not, they go to a second trial, second drug, and see what works best. If this testing process could instead be done on little organoids, it would be helpful.

Not just cardiac drugs, many chemotherapies have cardiac side effects. So rather than subjecting the patient to testing various cocktails of drugs, if we could get some information early on about whether a particular patient is more susceptible to a therapy, we can treat at a very granular, precise level for each patient, he says.

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How growing mini human hearts is advancing precision medicine, drug discovery - The Sociable

Research Roundup: Improving Current Immunotherapies and More – BioSpace

Improving on Current Immunotherapies

Researchers from the Wellcome Sanger Institute, GlaxoSmithKline and Biogen, working under the Open Targets initiative, have demonstrated that thousands of DNA differences that are associated with immune diseases are also connected to the specific switching on of a subtype of immune cells. Previous research has shown that there are thousands of genetic variants common in individuals with immune diseases. The new study was published in the journal Nature Genetics.

Our study is the first in-depth analysis of immune cells and cytokine signals in the context of genetic differences linked to immune diseases, said Blagoje Soskic, lead author of the paper from the Wellcome Sanger Institute and Open Targets. We found links between the disease variants and early activation of memory T-cells, suggesting that problems with regulating this early T-cell activation could lead to immune diseases.

The research teams evaluated parts of the genome active in three types of immune cells accumulated from healthy volunteers, then compared their positions against all the genetic variants associated to different immune diseases. They also added different cytokines to their pool, which then consisted of a total of 55 different cell states that mimic immune disease inflammation. One particular cell type and cell state, early activation of memory T-cells, had the most active DNA as the same regions as the genetic variants associated with immune diseases. Cytokines, however, did not have as significant a role as suspected.

There are thousands of different cell types and states in the body, and finding the cause of autoimmune diseases is like finding a needle in a haystack, said Gosia Trynka, senior author from Wellcome Sanger Institute and Open Targets. We have identified early activation of memory T-cells as being particularly relevant to immune diseases, and will now be able to dive deeper into studying how this is regulated, to discover genes and pathways that could be used as drug targets.

Treating Heart Attacks with an Injectable Hydrogen

Researchers at the University of California San Diego, showed that use of an injectable hydrogel was able to repair damage and restore heart function in patients after a heart attack. This was a Phase I clinical trial sponsored by Ventrix, a UCSD spin-off. The gel, named VentriGel, is manufactured from cardiac connective tissue from pigs. The researchers take the tissue, strip out heart muscle cells, then freeze-dry and grind it into powder, then liquefy into a fluid that allows it to be injected into the heart muscle without surgery. At room temperate the liquid become a semi-solid, porous gel.

The Chromosome Connections Between Humans and Archaebacteria

Archaebacteria are some of the oldest-living organisms on the planet, one of the three biological domains: bacteria, eukaryotes, and archaea. Researchers at the University of Indiana found that the way DNA is organized in archaeal chromosomes has more similarities to human DNA than it does to bacteria. They believe it may help scientists study human DNA and diseases more effectively because the archaea are similar but less complex than human DNA.

How the 2 Strands of DNA are Held Together

DNA is made up of two strands of sugar and phosphate molecules, twisted into a helix. It has been generally accepted that the two strands were held together by hydrogen bondswhich now appears to be incorrect. Researchers at Chalmers University of Technology, Sweden, showed that that molecules have a hydrophobic interior and exist in an environment mostly of watermeaning that the DNA molecules nitrogen basis are hydrophobic, pushing the surrounding water away. The hydrogen bonds appear be more involved in sorting the base pairs rather than connecting the two strands together.

Unexpected Amyotrophic Lateral Sclerosis Findings

Accumulation of a protein, TDP-43, in the brain has been linked to amyotrophic lateral sclerosis (ALS). Researchers used a technique called deep mutagenesis to study all possible mutations in the TDP-43 protein with unexpected results. They developed more than 50,000 mutations of TDP-43 and tracked their toxicity to yeast cells. However, instead of finding the mutant forms to be more toxic, they were less toxic, forming unusual liquid species in the cells. Although unclear, the researchers believe its possible that aggregation of TDP-43 is actually protective, rather than damaging.

Antimicrobial Resistance is Growing Dramatically Around the World

Researchers developed a map of the world showing incidences of antimicrobial activity. The overall picture is of a dramatic increase in antimicrobial resistance, with the highest rates in animals in northeast China, northeast India, southern Brazil, Iran and Turkey. Some of this is related to improved economies, leading to increased meat consumption, linked to dramatic increases in the use of antibiotics in farm animals, but in countries with lower rates of monitoring for antibiotic resistance.

Possible New Weapon for Use in Immunotherapy for Cancer: iNKT Cells

Invariant natural killer T-cells (iNKT) are not as common as other types of immune cells, but they are generally viewed as more powerful. Researchers at UCLA, working in mice, were able to harness iNKT cells to attack cancer cells. They genetically engineered hematopoietic stem cells to develop into iNKT cells, which they then tested on mice with both human bone marrow and human cancers and multiple myeloma and melanoma models. The stem cells differentiated normally into iNKT cells and continued to produce them for the rest of the animals lives. The stem cell-derived iNKT cells also effectively suppressed tumor growth.

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Research Roundup: Improving Current Immunotherapies and More - BioSpace

Researchers Build Microscopic Biohybrid Robots Propelled by Muscles and Nerves – ENGINEERING.com

Researchers Build Microscopic Biohybrid Robots Propelled by Muscles and NervesArnold Lander posted on September 27, 2019 |

An artistic rendering of a new generation of biobotssoft robotic devices powered by skeletal muscle tissue that is stimulated by onboard motor neurons. (Image courtesy of Michael Vincent.)

Researchers at the University of Illinois have developed a biohybrid robot powered by neuromuscular tissue that responds to light. Biohybrid robots are the result of integrating synthetic material and living tissue such as muscle, nerves or bone to produce a device that is capable of independent motion. The addition of neuronal action to control muscle tissue represents a significant step forward in the quest for autonomous biobots.

In 2014 researchers developed the first self-propelled biobots powered by cardiac muscle tissue taken from rats. These early designs, modeled after sperm cells, had a single tail and could swim but could not sense their environment or make decisions.

In this new study, computational models were used to optimize the skeleton design. The previous single-tailed structure was replaced with a new two-tailed model, and the length of the tails was also adjusted. These design improvements resulted in an order of magnitude increase in swimming speed from the previous single-tailed version.

The robot was completed by applying an optogenetic cell culture derived from mouse stem cells adjacent to the muscle tissue. In this process, the neurons advanced toward the muscle and formed neural muscular junctions, with the robot assembling entirely on its own.

The biobot team: (from left) Professor Tahir Saif, graduate student Omar Aydin, graduate student Xiastian Zhang, Professor Mattia Gazzola, graduate student Gelson J. Pagan-Diaz, and Dean of Granger College of Engineering, Rashid Bashir.

The success of this study helps set the stage for the future development of engineered, multicellular living systems with the ability to respond intelligently to environmental cues. These living machines could potentially find applications in the fields of bioengineering, medicine and material science.

The paper Neuromuscular actuation of biohybrid motile bots is availablehere.

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Researchers Build Microscopic Biohybrid Robots Propelled by Muscles and Nerves - ENGINEERING.com

Conjugated polymers optically regulate the fate of endothelial colony-forming cells – Science Advances

Abstract

The control of stem and progenitor cell fate is emerging as a compelling urgency for regenerative medicine. Here, we propose a innovative strategy to gain optical control of endothelial colony-forming cell fate, which represents the only known truly endothelial precursor showing robust in vitro proliferation and overwhelming vessel formation in vivo. We combine conjugated polymers, used as photo-actuators, with the advantages offered by optical stimulation over current electromechanical and chemical stimulation approaches. Light modulation provides unprecedented spatial and temporal resolution, permitting at the same time lower invasiveness and higher selectivity. We demonstrate that polymer-mediated optical excitation induces a robust enhancement of proliferation and lumen formation in vitro. We identify the underlying biophysical pathway as due to light-induced activation of TRPV1 channel. Altogether, our results represent an effective way to induce angiogenesis in vitro, which represents the proof of principle to improve the outcome of autologous cell-based therapy in vivo.

In recent years, organic semiconductors have emerged as highly promising materials in biotechnology, thanks to several key-enabling features. Differently from silicon-based electronics, they support both electronic and ionic charge transport (1); they can be easily functionalized with specific excitation and sensing capabilities (24); and they are solution processable, soft, and conformable (5). They are highly biocompatible, being suitable for in vivo implantation and long-term operation, as recently reported for many different applications, including electrocorticography, precise delivery of neurotransmitters, electrocardiography, deep brain stimulation, and spinal cord injury (69). An important, distinctive feature of organic semiconductors is their sensitivity to the visible and near-infrared light. Recently, our and other groups have exploited it for optical modulation of cell electrophysiological activity, by using conjugated polymers and organic molecules as exogenous light-sensitive actuators (1012). Interesting applications have been reported in the field of artificial visual prosthesis (5), photothermal excitation or inhibition of cellular activity (13, 14), and modulation of animal behavior (15).

In this framework, the opportunity to use polymer-based phototransduction mechanisms to regulate the very early stages of living cell development has been very scarcely considered (16, 17). The possibility to selectively and precisely regulate a number of cell processes, such as adhesion, differentiation, proliferation, and migration, would be key to regenerative medicine and drug screening. The presently dominant approaches to reliably regulate stem and progenitor cell fate for regenerative purposes mainly rely on the use of chemical cues. However, irreversibility and lack of spatial selectivity represent important limitations of these methods. Whenever targeting in vivo applications, one must face the major, unsolved problem of diffusion of neurotrophic molecules by the conventional intravenous or oral routes. In addition, the therapeutic outcome of autologous cell-based therapy is often impaired by low engraftment, survival, and poor integration of stem cells within the environment of the targeted tissue. Other stimuli, mainly consisting of mechanical and electrical cues, were recently reported to have some notable effects, and recent advances in nanotechnology and material science enabled versatile, robust, and larger-scale modulation of the cell fate. In particular, carbon-based materials and conjugated polymers led to interesting results (18). However, their distinctive visible light absorption was never exploited in optically driven techniques.

Use of light actuation has been proposed either by viral transfer of light-sensitive proteins, by optogenetics tools, or by absorption of endogenously expressed light-sensitive moieties, based on low lightlevel therapies (1921). In the first case, interesting results were obtained (22); however, this approach bears all the drawbacks related to the need for viral gene transfer. Photobiomodulation led to interesting outputs as well, but overall efficiency is hampered by the limited absorption of light-responsive molecules endogenously expressed in living cells.

In this work, we propose to couple the use of conjugated polymers with visible light excitation to gain optical control of cell fate. We focus our attention on endothelial progenitor cells (EPCs) and, in particular, on endothelial colony-forming cells (ECFCs), which are currently considered the bona fide best surrogate of EPCs (23). ECFCs are mobilized from the bone marrow and vascular stem cell niche to reconstruct the vascular network destroyed by an ischemic insult and to restore local blood perfusion (24). ECFCs may be easily harvested from peripheral blood, display robust clonogenic potential, exhibit tube-forming capacity in vitro, and generate vessel-like structures in vivo (24, 25), thereby representing a promising candidate for autologous cell-based therapy of ischemic disorders (24). Manipulating the signaling pathways that drive ECFC proliferation, migration, differentiation, and tubulogenesis could represent a reliable strategy to improve the regenerative outcome of therapeutic angiogenesis in the harsh microenvironment of an ischemic tissue, such as the infarcted heart (24, 25). Intracellular Ca2+ signals play a crucial role in stimulating ECFC proliferation and tubulogenesis by promoting the nuclear translocation of the Ca2+-sensitive nuclear transcription factor B (NF-B) (2628). It has, therefore, been suggested that intracellular Ca2+ signaling could be targeted to boost the regenerative potential of autologous ECFCs for regenerative purposes (29). For the above-mentioned reasons, ECFCs represent a valuable test bed model for assessing the possibility to exploit the visible light sensitivity of conjugated polymers to gain touchless, optical modulation of cell proliferation and function.

In this framework, we demonstrate that polymer-mediated optical excitation during the first steps of ECFC growth leads to a robust enhancement of both proliferation and tubulogenesis through the optical modulation of the Ca2+-permeable transient receptor potential vanilloid 1 (TRPV1) channel and NF-Bmediated gene expression. Our results represent, to the best of our knowledge, the first report on the use of polymer photoexcitation for the in vitro modulation of ECFC fate and function, thereby representing the proof of principle to obtain direct control of progenitor cell fate.

Figure 1A shows a sketch of the bio/polymer interface developed for obtaining optical control of ECFC proliferation and network formation, together with the polymer chemical structure and the optical absorption spectrum. The material of choice for light absorption and phototransduction is a workhorse organic semiconductor, widely used in photovoltaic and photodetection applications, namely, regioregular poly(3-hexyl-thiophene) (P3HT) (6). It is characterized by a broad optical absorption spectrum, in the blue-green visible region, peaking at 520 nm. P3HT outstanding biocompatibility properties have been reported in a number of different systems, both in vitro and in vivo, including astrocytes (30), primary neurons and brain slices (14), and invertebrate models of Hydra vulgaris (15). Chronical implantation of P3HT-based devices in the rat subretinal space did not show substantial inflammatory reactions up to 6 months in vivo (10). Here, polymer thin films (approximate thickness, 150 nm) have been deposited by spin coating on top of polished glass substrates, as detailed in Materials and Methods. Both polymer-coated and glass substrates have been thermally sterilized (120C, 2 hours), coated with fibronectin, and, lastly, used as light-sensitive and control cell culturing substrates, respectively. ECFCs have been isolated from peripheral blood samples of human volunteers and seeded on top of polymer and glass substrates.

(A) P3HT polymer optical absorption spectrum. Insets show the chemical structure of the conjugated polymer and a sketch of the polymer device used for cell optical activation. ECFCs are cultured on top of P3HT thin films, deposited on glass substrates. (B) ECFC viability at fixed time points after plating (24, 48, and 72 hours). Cell cultures were kept in dark conditions at controlled temperature (37C) and fixed CO2 levels (5%). No statistically significant difference was observed between the glass and polymer substrates at any fixed time point (unpaired Students t test). (C) Experimental setup and optical excitation protocol for evaluation of polymer-mediated cell photoexcitation effects on cell fate. Polymer and control samples are positioned within a sterilized, home-designed petri holder. Light scattering effects are completely screened. The geometry and the photoexcitation protocol have been implemented to minimize overheating effects and to keep the overall extracellular bath temperature fairly unaltered. Thirty-millisecond-long green light pulses are followed by 70 ms in dark condition.

ECFC proliferation on polymer substrates has been primarily assessed in dark conditions at three different time points, namely, 24, 48, and 72 hours after plating (Fig. 1B). Polymer-coated samples, while showing from the very beginning a slightly lower number of cells as compared with control substrates, exhibit a proliferation rate fully similar to cells plated on glass substrates (slope of the linear fitting is 0.034 0.003, R2 = 0.99 and 0.034 0.005, R2 = 0.96 for control and P3HT polymer samples, respectively).

Once assessed that the P3HT polymer surface represents a nicely biocompatible substrate for ECFC seeding and proliferation in the dark, we moved to investigate the effect of polymer photoexcitation. In more detail, to evaluate the effect of optical stimulation on cell proliferation and network formation, we continuously shined light for the whole temporal window required for cell growth, and we realized an ad hoc system suitable for operation within the cell incubator. The experimental configuration and the excitation protocol are schematically represented in Fig. 1C. Optical excitation is provided by a light-emitting diode (LED) source, with maximum emission wavelength at 525 nm, incident from the substrate side. The choice of the protocol, continuously administered to the cell cultures during early seeding and proliferation stages, has been mainly dictated by the need to avoid overheating effects, with possible negative outcomes on the overall cell culture viability. On the basis of these considerations, we opted for a protocol based on 30-ms excitation pulses, followed by a 70-ms dark condition, at a photoexcitation density of 40 mW/cm2. The whole protocol is continuously repeated for a minimum of 4 up to 36 hours, depending on the type of functional assay, at controlled temperature (37C) and CO2 levels (5%).

The temporally precise and spatially localized measurement of the temperature variation upon polymer photoexcitation at the polymer/cell interface (i.e., within the cell cleft) is not straightforward because it requires the use of localized, submicrometer probes with a fast response time. However, according to the heat diffusion equation, we expect that dissipation occurs within a few milliseconds, following exponential decrease dynamics (14). Moreover, we used the well-known method of the calibrated pipette (31) to characterize the temperature variation dynamics within the extracellular bath volume, defined by the cylinder with the base area corresponding to the light spot size and the height of about 1 m. This choice is a good approximation of the overall volume occupied by a single ECFC cell; thus, it provides a realistic estimation of the average heating experienced by the cell (fig. S1A). We observe that temperature variation closely follows short optical pulse dynamics, reaching a maximum temperature at the end of the 30-ms illumination period, quickly followed by an almost complete thermal relaxation to the basal temperature during the 70-ms-long dark period. We conclude that our polymer-based system provides a highly spatially and temporally resolved method for optical excitation, making it possible, in perspective, to selectively target single cells and even cell subcompartments. Upon prolonged illumination (hours), one should also consider possible overheating effects of the whole extracellular medium volume. The average temperature of the bath for the entire duration of the long-term experiment was measured by a thermocouple immersed in the medium. Data show that an equilibrium situation is established after 5 hours and that the absolute temperature of the bath is increased by about 1.5 (fig. S1B). The adopted prolonged excitation protocol does not negatively affect overall cell culture viability (see below).

Figure 2 reports specific effects mediated by P3HT substrates and visible light stimulation on ECFC proliferation. ECFCs were plated in the presence of EGM-2 medium to facilitate the adhesion to the substrate. After 12 hours, the medium was switched to EBM-2 supplemented with 2% fetal bovine serum, and the cells were subjected to the long-term lighting protocol for 36 hours at controlled temperature (37C) and CO2 levels (5%). Under these conditions, ECFCs seeded on P3HT and subjected to light stimulation undergo a significant increase in proliferation rate, as compared with the control condition, i.e., to cells also seeded on P3HT polymer substrates but kept in dark conditions for the whole duration of the experiment (+158% versus P3HT dark; P < 0.05). No statistically significant difference in proliferation was observed among cells seeded on glass, whether they were subjected to optical excitation or not (Fig. 2A).

(A) Relative variation of the proliferation rate of ECFCs subjected to long-term optical excitation seeded on both bare glass and P3HT thin films, together with corresponding control samples kept in dark conditions. Cell proliferation was measured after 36 hours of culture in the presence of EBM-2 supplemented with 2% fetal calf serum. (B) Relative variation of the proliferation rate of ECFCs subjected to long-term optical excitation seeded on P3HT in the absence (CTRL) and presence of 10 M capsazepine (CPZ), 10 M ruthenium red (RR), 20 M RN-1734 (RN-1734), and 30 M BAPTA-AM (BAPTA). The results are represented as the means standard error of the mean (SEM) of three different experiments conducted on cells harvested from three different donors. The significance of differences was evaluated with one-way analysis of variance (ANOVA) coupled with Tukey (A) or Dunnetts (B) post hoc test. *P < 0.05.

Recent evidence demonstrated an interesting correlation between processes key to ECFC vascular regeneration, including proliferation and network formation, and activation of TRPV1 channels, which are expected to be endogenously expressed in ECFCs (32). In addition, we recently reported that polymer photoexcitation leads to selective TRPV1 activation in transfected human embryonic kidney (HEK) cell models (33). Therefore, we were prompted to evaluate whether the increase in cell proliferation is distinctively determined by a polymer-mediated photoactivation of the TRPV1 channel. To this goal, we preliminarily checked the actual expression of the TRPV1 channel in the ECFC models by carrying out electrophysiology experiments in patch-clamp configuration. Methods and results are extensively discussed in the Supplementary Materials (fig. S2 and related description). Briefly, the expression of the TRPV1 channel was confirmed, as well as the capability to selectively excite its activity through localized polymer excitation at high optical power density. To establish whether the TRPV1 channel also has a role in the observed increase in cell proliferation upon polymer excitation, we performed the experiments under light illumination upon administration of a highly specific TRPV1 antagonist [capsazepine (CPZ), 10 M], an aspecific TRPV channel inhibitor [ruthenium red (RR), 10 M], and a selective antagonist of a different temperature-sensitive channel, TRPV4, which is also endogenously expressed in ECFCs (RN-1734, 20 M) (34) (Fig. 2B). TRPV1 inactivation by CPZ and RR results in a relative, strong reduction in cell proliferation by 51 and 30%, respectively, as compared with untreated cells. Conversely, in the case of RN-1734 treatment, the proliferation increase due to polymer photoexcitation is completely unaltered.

As mentioned earlier, intracellular Ca2+ signaling has been reported to drive ECFC proliferation (26, 28). To further investigate whether TRPV1-mediated extracellular Ca2+ entry mediates the proangiogenic response to light illumination, we pretreated ECFCs with [1,2-Bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester) BAPTA-AM] (30 M), a membrane-permeable buffer of intracellular Ca2+ levels (26, 28). BAPTA-AM is widely used to prevent the increase in intracellular Ca2+ concentration ([Ca2+]i) induced by extracellular stimuli and inhibits the downstream Ca2+-dependent processes. For instance, BAPTA-AM represents the most suitable tool to prevent the activation of Ca2+-sensitive decoders residing within tens of nanometers from the inner pore of plasmalemmal Ca2+ channels (35). It was recently reported that, in the absence of Ca2+-mobilizing growth factors, it does not impair the low rate of ECFC growth (27). Here, however, BAPTA-AM clearly reduced the light-driven proliferation increase, thus confirming that TRPV1 stimulates ECFCs through an increase in [Ca2+]i (Fig. 2B).

We further examined the physiological outcome of chronic light stimulation by carrying out a tube formation assay within an extracellular matrix protein-based scaffold, which is a surrogate of the basement membrane extracellular matrix. This assay recapitulates many steps of the angiogenic process, including adhesion, migration, protease activity, and tubule formation (27, 28). ECFCs were plated in the presence of EBM-2 medium supplemented with 2% fetal calf serum and subjected to the long-term lighting protocol for 8 hours at controlled levels of temperature and CO2. Control experiments carried out in dark conditions, either onto glass (see Fig. 3A for a representative optical image) or onto polymer substrates (Fig. 3C), as well as control experiments carried out upon photoexcitation of cells seeded on glass substrates (Fig. 3B), do not show remarkable differences. Conversely, ECFC cultures subjected to polymer-mediated optical excitation clearly tend to assemble into an extended bidimensional capillary-like network (Fig. 3D). Cell cultures were monitored up to 24 hours after illumination onset, but results were comparable to observations reported here, after 8 hours of illumination. This qualitative observation is fully confirmed by quantitative morphological analysis (27). As depicted in the sketch of Fig. 3E, we quantitatively evaluated the main features typical of the capillary-like network formation and, in particular, the number of master segments (Fig. 3F), master junctions (Fig. 3G), and meshes (Fig. 3H). In all cases, a notable, statistically relevant difference is observed between cells subjected to polymer-mediated optical excitation and controls. Within the same considered temporal window, the combined use of polymer substrates and visible light stimuli does not lead to sizable toxicity effects or delays in cell proliferation. Conversely, it leads to enhanced cell proliferation (Fig. 2) and allows the achievement of the formation of a more extended and mature tubular network (Fig. 3).

(A to D) Representative images of in vitro tubular networks of ECFCs subjected to long-term optical excitation seeded on both bare glass and P3HT, as well as on corresponding control samples in dark conditions. Cultures were observed up to 24 hours, but their appearance did not substantially change after pictures were taken after 8-hour culture. Scale bars, 250 m. (E) Sketch representing the main features typical of the capillary-like network that were considered for the topologic analysis. Number of master segments (F), master junctions (G), and meshes (H) analyzed in the different conditions. The results are represented as the means SEM of three different experiments conducted on cells harvested from three different donors. The significance of differences was evaluated with one-way ANOVA coupled with Tukey post hoc test. **P < 0.01 and ***P < 0.001.

As evidenced for the proliferation rate, the TRPV1 channel activation emerges to play also a fundamental role in tubulogenesis (Fig. 4). The TRPV1 pharmacological blockade with the specific inhibitor CPZ deterministically leads to a marked reduction in network formation (Fig. 4A). Upon CPZ administration, a statistically significant decrease in the relative variation of the number of master segments (Fig. 4E), master junctions (Fig. 4F), and meshes (Fig. 4G) is observed. In line with the results shown in Figs. 2 and 3, RR administration resulted in a less marked but still sizable reduction in the tubular network (Fig. 4, B and E to G), probably due to the minor specificity toward TRPV1, while the protubular effect of light remained fully unaltered in the presence of the TRPV4 inhibitor RN-1734 (Fig. 4, C and E to G). Notably, the treatment with BAPTA-AM (30 M), which affected ECFC proliferation, was able to prevent also in vitro tubulogenesis, thus corroborating the key role of intracellular Ca2+ signaling in the proangiogenic response to light illumination (Fig. 4, D and E to G). Control measurements carried out in dark conditions on polymer substrates upon the considered pharmacological treatments do not show any relevant effect (fig. S4, A to C). Overall, this evidence supports the notion that TRPV1 stimulates ECFC proliferation and network formation and demonstrates that optical excitation, properly mediated by biocompatible polymer substrates, positively affects ECFC fate by spatially and temporally selective activation of the TRPV1 channel.

(A to D) Representative optical images of in vitro tubular network of ECFCs subjected to long-term optical excitation seeded either on bare glass or on P3HT thin films and treated respectively with CPZ (A), RR (B), RN-1734 (C), and BAPTA-AM (D). Scale bars, 250 m. (E to G) Relative variation of number of master segments (E), master junctions (F), and meshes (G) of ECFCs subjected to long-term optical excitation seeded on P3HT in the absence [control (CTRL)] and presence of 10 M CPZ, 10 M RR, 20 M RN-1734 (RN-1734), and 30 M BAPTA-AM (BAPTA). The results are represented as the means SEM of three different experiments conducted on cells harvested from three different donors. The significance of differences was evaluated with one-way ANOVA coupled with Dunnetts post hoc test. *P < 0.05 and **P < 0.01.

We now turn our attention to elucidating the possible mechanisms leading to optically enhanced tubulogenesis, through TRPV1 channel activation, upon prolonged polymer excitation.

Reliable optical modulation of the cell activity mediated by polymer photoexcitation has been reported in several, previous reports, both in vitro, at the level of single cells, and in vivo, at the level of the whole animal, as evidenced by behavioral studies on both invertebrate and vertebrate models. Three different photostimulation mechanisms, active at the polymer/cell interface, have been proposed so far. These include (i) the creation of an interface capacitance, i.e., of a localized electric field, possibly affecting the cell membrane potential (11); (ii) photothermal processes, establishing a localized temperature increase upon polymer photoexcitation (13, 36); and (iii) photoelectrochemical reactions, mainly oxygen reduction processes, leading to a local variation of extracellular and/or intracellular pH (33) and sizable production of reactive oxygen species (ROS), at a nontoxic concentration, and intracellular calcium modulation (37).

In electrophysiological experiments, carried out at a photoexcitation density higher than the one used in chronic stimulation by about two orders of magnitude, we clearly observe TRPV1 excitation, corresponding however to a small variation of the cell membrane potential, in the order of a few millivolts (Supplementary Materials). Thus, upon much lower light intensity, the effects of either direct photothermal channel activation and of photocapacitive charging are expected to be negligible. To further corroborate this hypothesis, we carry out control experiments aimed at disentangling photoelectrical from photothermal transduction processes.

First, we use a different material as a cell-seeding substrate, characterized by optical absorption and heat conductivity similar to the ones typical of P3HT (13) but fully electrically inert (i.e., unable to sustain electronic charge generation upon photoexcitation). The material of choice is a photoresist (MicroPosit S1813). S1813 thin films are realized by spin coating, and deposition parameters are optimized to obtain optical absorbance values similar to the semiconducting polymer samples at the considered excitation wavelength. The capability of photoresist substrates to sustain ECFC proliferation was successfully assessed in a control measurement, obtaining fully comparable results with respect to the P3HT substrates (Fig. 5A). The functional effect eventually driven by photoresist optical excitation on tubulogenesis was then investigated by using the same experimental conditions and analysis technique previously adopted for polymer and glass substrates (Fig. 5B). Data show that long-term photoresist excitation does not lead to sizable enhancement of the cellular network formation, thus pointing out that a purely photothermal effect does not play a major role in boosting the tubulogenesis process at variance with semiconducting polymer substrates. In a complementary experiment, we directly assessed the occurrence of photoelectrochemical reactions at the polymer/extracellular bath interface by measuring ROS production. We previously demonstrated that P3HT polymer thin films exposed to saline electrolytes sustain efficient light-triggered charge generation and charge transfer processes, giving rise to photoelectrochemical reactions (38, 39). Moreover, we also reported that P3HT nanoparticles are efficiently internalized within the cytosol of secondary line cell models (HEK-293) and that their photoexcitation leads to the production of ROS and subsequent intracellular calcium modulation (15, 37). However, the actual capability to sustain photoelectrochemical reactions in the specific experimental conditions used in this work (polymer film deposition conditions, sterilization process, prolonged exposure to specific cellular growth medium in an incubating environment, prolonged exposure to a light excitation protocol, light wavelength, pulses duty cycle, and power density) was never assessed. In particular, direct measurement of intracellular ROS was never carried out in the presence of polymer thin films. To this goal, we realized ECFC cultures on top of polymer and glass control substrates, and we exposed them to the same optical stimulation protocol previously used in the tubulogenesis assay. ROS production was then evaluated by means of a fluorescence experiment based on the use of the well-known ROS probe 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA) (Fig. 5C). Results show that light induces an increase in ROS production both on glass and polymer substrates. Relative percentage variation amounts to +34 and +200%, respectively, thus pointing out that polymer surface photocatalytic activity plays a major role in the phototransduction phenomenon.

(A) An electrically insulating, thermally conducting material (photoresist) is successfully used as an ECFC seeding substrate. (B) Photoresist long-term photoexcitation does not lead to sizable enhancement in tubulogenesis parameters. (C) Evaluation of intracellular ROS production following long-term photoexcitation protocol of ECFC cultures on polymer and glass substrates (glass dark, n = 629; glass light, n = 656; P3HT dark, n = 686; and P3HT light, n = 583). For each panel, the results are represented as the means SEM of three different experiments conducted on cells harvested from three different donors. The significance of differences was evaluated with unpaired Students t test (A and B) or one-way ANOVA coupled with Tukey post hoc test (C). ***P < 0.001.

Altogether, data in Fig. 5 indicate that photoelectrochemical reactions induced by light at the interface between the organic semiconducting polymer and the extracellular bath play a key role in triggering the observed enhancement in cell network formation through indirect activation of the TRPV1 channel. The occurrence of faradaic phenomena at the polymer/bath interface may give rise to material degradation effects. The photostability of the polymer substrates was carefully checked by optical absorption, photoluminescence, and Raman spectra measurements. By treating the samples with the same experimental protocol used for cell tubulogenesis assays (photoexcitation density, pulses frequency, overall exposure duration, temperature, and humidity levels), no sign of irreversible polymer degradation was observed, as compared with nonilluminated samples (fig. S5).

The Ca2+-sensitive transcription factor NF-B might provide the missing link between the influx of Ca2+ through TRPV1 and the increase in proliferation and tubulogenesis observed in ECFCs upon photostimulation (26). We therefore monitored the nuclear translocation of the cytoplasmic p65 NF-B subunit via immunofluorescence staining and mRNA levels of a number of genes induced during tubulogenesis in an NF-Bdependent manner (26, 40) (Fig. 6). Our data indicate that ECFCs seeded on polymer and subjected to light stimulation have a significantly enhanced p65 NF-B nuclear translocation compared with the control conditions consisting of cells also seeded on P3HT but kept in dark conditions (+35% versus P3HT dark; P < 0.05; Fig. 6, A and B), and seeded on bare glass (+28% versus glass dark; P < 0.05; Fig. 6B). No differences were observed between samples seeded on glass, whether they were subjected to optical excitation or not (fig. S6).

ECFCs seeded on P3HT samples and glass controls are subjected to long-term photostimulation protocol. Corresponding control samples are kept in dark conditions. After photostimulation, p65 NF-B nuclear translocation (A and B) and mRNA levels of tubulogenic/angiogenic genes that have been shown to be activated downstream of NF-B (C) are evaluated. (A) Representative images of immunofluorescence staining showing p65 NF-B (green) nuclear translocation. Cell nuclei are detected by 4,6-diamidino-2-phenylindole (DAPI) (blue). Scale bars, 50 m. (B) Quantitative evaluation of p65 NF-B nuclear translocation, as evidenced by colocalization experiments. Results are expressed as means SEM of the relative percentage of p65 nucleipositively stained cells to the total number of cells (glass dark, n = 151; glass light, n = 125; P3HT dark, n = 147; and P3HT light, n = 159). Ten fields per condition are analyzed. Data are obtained from two different experiments conducted on cells harvested from two different donors. (C) mRNA levels of intercellular adhesion molecule 1 (ICAM1), selectin E (SELE), and matrix metalloproteinases (MMP1, MMP2, and MMP9) are quantified by real-time polymerase chain reaction (PCR). Data are expressed as means SEM of percentage variation with respect to cells grown in the dark (n = 6). The significance of differences was evaluated with unpaired Students t test (C) or one-way ANOVA coupled with Tukey post hoc test (B). *P < 0.05 and **P < 0.01.

In addition, we have checked the expression of nine genes whose expression is known to be induced in endothelial cells during tubulogenesis/angiogenesis in an NF-Bdependent manner. We considered intercellular adhesion molecule 1 (ICAM1); vascular adhesion molecule 1 (VCAM1); selectin E (SELE), matrix metalloproteinases (MMPs) 1, 2, and 9; vascular endothelial growth factor A (VEGFA); cyclooxygenase 2 (COX2, PTGS2); and cyclin D1 (CCND1) (40). Of these, five are significantly up-regulated by light exposure in cells grown on P3HT substrates, namely, ICAM1 (+90% versus P3HT dark; P < 0.05), SELE (+1119%; P < 0.01), MMP1 (+242%; P < 0.01), MMP2 (+467%; P < 0.05), and MMP9 (+458%; P < 0.05) (Fig. 6C). Conversely, VCAM1, VEGFA, PTGS2, and CCND1 do not show relevant variation upon light stimulation (fig. S7A). Light excitation on cells grown on bare glass substrates does not show any significant effect as compared with control samples in dark conditions (fig. S7B).

Therapeutic angiogenesis via autologous EPC transplantation represents a promising strategy to preserve or, at least, partially restore cardiac function after myocardial infarction (24, 41). Nevertheless, the regenerative outcome of EPC-based therapies in preclinical studies was rather disappointing and did not lead to sufficient neovascularization of the ischemic heart (41). This led to the proposal to boost their angiogenic activity by using emerging technologies, including tissue engineering of vascular niches, pharmacological preconditioning, or genetic and epigenetic reprogramming (42). ECFCs are regarded among the most suitable EPC subtypes to induce therapeutic angiogenesis and cardiac regeneration due to their high clonal proliferative potential and ability to assemble into capillary-like structures (23, 24). In addition, they can be easily isolated and expanded from the peripheral blood of patients and healthy donors. It has recently been suggested that their angiogenic activity could be boosted by targeting the intracellular Ca2+ toolkit (29). Here, we target ECFCs by adopting a fully different approach, i.e., by exploiting visible light as a modulation trigger and by the use of a thiophene-based conjugated polymer as the exogenous, light-responsive actuator. We demonstrate that photoexcitation of the organic material deterministically leads to robustly enhanced proliferation and tubulogenesis. Pharmacological assays, supported by electrophysiology experiments, allow the identification of TRPV1 selective excitation as a key player in the molecular pathway leading to macroscopic outcomes, as observed by quantitative analysis of the angiogenic response.

All data unambiguously show that polymer photoexcitation leads to selective activation of the TRPV1 channel, which has recently been shown to be expressed and drive angiogenesis in human ECFCs (32). TRPV1 is a polymodal Ca2+-permeable channel that integrates multiple chemical and physical cues to sense major changes in the local microenvironment of most mammalian cells (43). TRPV1 is activated by either noxious heat (>42C) and acidic solutions (pH < 6.5), whereas mild acidification (pH 6.3) of the extracellular milieus sensitizes TRPV1 to heat stimulation and results in channel activation at temperature thresholds (30 to 32C) well below the normal one (43). ROS production is also expected to further contribute to TRPV1 activation, as previously reported in mouse coronary endothelial cells (44), in which hydrogen peroxide elicits a depolarizing inward current at negative holding potentials. Likewise, ROS may stimulate TRPV1 to depolarize the membrane potential, thereby triggering trains of action potentials in airway C fibers (45, 46).

On the basis of measurements carried out in cells seeded on the photoresist substrate, as well as on direct evaluation of a limited, local temperature increase upon light stimuli during the long-term photoexcitation protocol, we infer that the excitation of the TRPV1 channel through direct photothermal transduction is not the predominant process leading to enhanced tubulogenesis.

We have previously demonstrated that polymer photoexcitation leads to generation of faradaic current, to electron transfer reactions at the polymer/electrolyte interface, and to sizable intracellular enhancement of ROS (37, 38). Briefly, optical excitation of P3HT polymer thin films leads to photoexcited species (Eq. 1), namely, singlets and charge states, which react with the oxygen dissolved in the cell medium, thus reducing oxygen (Eq. 2)P3HT+hP3HT*(1)P3HT*+O2P3HT++O2(2)

The superoxide further evolves, leading to the generation of different ROS and, lastly, ending up with hydrogen peroxide production. It has been reported that extracellular H2O2 can cross the plasma membrane through aquaporin AQP3, thereby triggering intracellular ROS signaling (47, 48). In line with our previous results, we have demonstrated here that intracellular ROS enhancement does occur in ECFCs upon photoexcitation of polymer thin films, thus contributing to TRPV1 activation.

Altogether, the evidence supports the hypothesis of a transduction mechanism mainly governed by photoelectrochemical reactions. Moreover, these same observations could explain why TRPV4, which is also expressed in ECFCs (34), is not sensitive to optical modulation. Although TRPV4 is activated by moderate heat (24 to 38C), it is supposed to be inhibited by local pH variation, although this is still a matter of debate (49, 50).

On the one hand, the role attributed in the phototransduction mechanism to the capability of the polymer to generate and transport electronic charges, as well as to its photocatalytic activity in an aqueous environment, clearly implies the need for a biocompatible, visible lightresponsive, semiconducting material. This excludes any possible implementation of the reported technique by using a thermally conducting, electrically insulating plastic substrate. Suitable cell-seeding materials have to be selected and developed within the wide arena of organic semiconducting polymers. On the other hand, the key role played by ROS raises additional issues about material photostability, cell viability, and overall safety and reliability of the technique. We extensively verified that the main polymer optoelectronic properties are not substantially altered by the exposure to light and to incubating conditions. From the biological point of view, it is very well known that high ROS levels can induce highly toxic effects and, finally, lead to cell death. We notice, however, that the established photoactivation protocol (illuminator geometry and air flow, light photoexcitation density, duty cycle, and repetition rate) has been implemented to avoid any detrimental effect. Accordingly, no toxicity effects were detected for the overall duration of the experiments, as proven by the robust increase in ECFC proliferation and tubulogenesis exposed to light. This observation is consistent with the emerging notion that appropriate ROS levels can exert a signaling role and control angiogenesis in endothelial cells (51).

The biophysical mechanisms whereby the photoactivation of TRPV1 stimulates in vitro angiogenesis in ECFCs deserve a more detailed discussion as well. Earlier work showed that TRPV1 stimulates proliferation and tube formation in vascular endothelial cells by mediating extracellular Ca2+ entry. The following increase in intracellular Ca2+ concentration ([Ca2+]i) leads to the recruitment of several downstream Ca2+-dependent decoders, such as endothelial nitric oxide synthase and Ca2+/calmodulin-dependent protein kinase II (CaMKII) (52). Recently, TRPV1 was found to induce also proliferation and tube formation in ECFCs by mediating the uptake of the endocannabinoid anandamide (32). This study, however, did not investigate whether TRPV1 activation was per se able to stimulate ECFCs by engaging Ca2+-dependent pathways. Intracellular Ca2+ signaling is a crucial determinant of ECFC fate and behavior (2628). Accordingly, light-induced ECFC proliferation and tube formation were markedly reduced by the pharmacological blockade of TRPV1-mediated Ca2+ entry with CPZ and RR and by preventing the subsequent increase in [Ca2+]i with BAPTA-AM. This finding endorses the view that optical excitation stimulates ECFCs through TRPV1-mediated extracellular Ca2+ entry, and we suggest here that this occurs via downstream activation of transcriptional factor NF-B. NF-B has previously been shown to stimulate cell proliferation and tubulogenesis in endothelial cells (53, 54) and in hepatocytes (55). Our group has shown that NF-B triggers the transcriptional program underlying the angiogenic response to extracellular Ca2+ entry in ECFCs (26). Moreover, NF-B activation in response to extracellular stimulation and Ca2+ entry through TRPV1 has also been demonstrated (56, 57). Under resting conditions, NF-B is retained in the cytoplasm by the complex with the inhibitory protein IB. An increase in [Ca2+]i results in IB degradation by ubiquitination, which is triggered upon the Ca2+-dependent phosphorylation of IB. As a consequence, the p65 NF-B subunit is released from IB inhibition and translocates into the nucleus (58) where it induces the expression of multiple proangiogenic genes (40). Consistently, we found that optical excitation significantly boosted the nuclear translocation of p65 in ECFCs cultured on the conjugated polymer compared with those not exposed to light. Robust up-regulation of several angiogenic genes, such as ICAM, SELE, MMP1, MMP2, and MMP9, which are under NF-Bdependent transcriptional control, was also consequently observed. Intriguingly, NF-B also mediates VEGFA-induced gene expression and angiogenesis in vascular endothelial cells (59, 60) through an increase in [Ca2+]i (61). These observations strongly hint at NF-B as the Ca2+-sensitive decoder that translates optical excitation into an angiogenic response in human ECFCs interfaced with the light-sensitive conjugated polymer.

Overall, our findings represent the proof of principle that optical modulation may be successfully exploited to directly control the fate of a progenitor cell population, i.e., ECFCs, which has been shown to support revascularization of ischemic tissues. The in vitro activation of ECFC angiogenic activity is made possible by the use of a biocompatible, light-sensitive polymer as the phototransduction element.

The combined use of optical excitation and organic polymer technology can open interesting perspectives for several different reasons. First, the use of light modulation allows unprecedented spatial and temporal resolution to be achieved in a fully reversible way. Light temporal and spatial patterns can be specifically designed and adapted to different in vitro cell models, allowing ideally endless combinations of possibilities, to finely tune overall output in cell proliferation and network formation. The demonstrated technology is minimally invasive, allows for massive parallelization of experiments, and can be virtually implemented in any cell therapy model in a straightforward way. In addition, the use of different polymers, with lower energy gap and in the form of nanobeads, may pave the way to the optical enhancement of therapeutic angiogenesis in vivo. Further work is needed to understand whether the pattern and/or intensity of the illumination protocol may be adjusted to further boost the angiogenic response. For instance, the optical excitation protocol consisted of 30-ms-long light pulses that were delivered at 1 Hz for 4 (tubulogenesis) up to 36 (proliferation) hours. This is likely to result in oscillations in [Ca2+]i, which are known to deliver the most instructive signal for ECFCs to undergo angiogenesis by inducing the nuclear translocation of the p65 NF-B subunit (26). As the frequency of intracellular Ca2+ oscillations can be artificially manipulated to regulate NF-Bdependent gene expression in virtually any cell type (62), we envisage an additional layer of specificity and control that could be exploited to further improve the angiogenic response to optical excitation. Future work will also be devoted to assess the outcome of optical modulation on patient-derived ECFCs. One of the main hurdles associated to autologous cell-based therapy is the impairment of the angiogenic activity of EPCs, including ECFCs harvested from cardiovascular patients (29). The therapeutic translation of our findings will require the demonstration that light-induced TRPV1 activation boosts angiogenesis also in ECFCs derived from individuals affected by severe cardiovascular disorders, such as hypertension, atherosclerosis, and heart failure. In this view, the combination of organic semiconductors and genetic manipulation to increase endogenous TRPV1 expression could be sufficient to restore the reparative phenotype of autologous ECFCs from cardiovascular patients.

Regioregular P3HT (99.995% purity; Mn 54,000 to 75,000 molecular weight) was purchased from Sigma-Aldrich and used without any further purification. The samples for cell cultures were prepared by spin coating on a square 18 mm by 18 mm glass (VWR International) substrates carefully rinsed in subsequent ultrasonic baths of ultrapure water, acetone, and isopropanol. P3HT solution was prepared in chlorobenzene at a final P3HT concentration of 20 g/liter and spin coated on the cleaned substrates with a two-step recipe: (i) 3 s at 800 rpm and (ii) 60 s at 1600 rpm. Polymer film thickness is about 150 nm.

Microposit S1813 photoresist was purchased from Shipley and used without any further purification. Photoresist thin films were prepared by spin coating on cleaned substrates with a two-step recipe: (i) 3 min at 300 rpm and (ii) 30 s at 2600 rpm. Parameters were adjusted to obtain homogeneous films and similar optical absorbance to the one of the polymer thin films, at the same excitation wavelength used in the long-term stimulation protocol (see below). All films were thermally treated in an oven at 120C for 2 hours for annealing and sterilization. To promote adhesion, samples were coated with fibronectin (from bovine plasma; Sigma-Aldrich) at a concentration of 2 mg/ml in phosphate-buffered saline (PBS) for at least 30 min at 37C and then rinsed with PBS.

ECFCs were isolated from peripheral blood and expanded as shown elsewhere (26). Blood samples (40 ml) collected in EDTA-containing tubes were obtained from healthy male human volunteers aged from 28 to 38 years. The Institutional Review Board at Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation in Pavia approved all protocols and specifically approved this study. Informed written consent was obtained according to the Declaration of Helsinki of 1975 as revised in 2008. We focused on the so-called ECFCs, a subgroup of EPCs that are found in the CD34+ CD45 fraction of circulating mononuclear cells (MNCs), exhibit robust proliferative potential, and form capillary-like structures in vitro (23). To isolate ECFCs, MNCs were obtained from peripheral blood by density gradient centrifugation on lymphocyte separation medium for 30 min at 400g and washed twice in EBM-2 with 2% fetal calf serum. A median of 36 106 MNCs (range, 18 to 66) was plated on fibronectin-coated culture dishes (BD Biosciences) in the presence of the endothelial cell growth medium EGM-2 MV (Lonza) containing endothelial basal medium (EBM-2), 5% fetal bovine serum (FBS), recombinant human (rh) EGF, rhVEGF, recombinant human Fibroblast Growth Factor-Basic (rhFGF-B), recombinant human Insulin-like Growth Factor-1 (rhIGF-1), ascorbic acid, and heparin and maintained at 37C in 5% CO2 and humidified atmosphere. Nonadherent cells were discarded after 2 days, and thereafter, medium was changed three times a week. The outgrowth of ECFCs from adherent MNCs was characterized by the formation of a cluster of cobblestone-shaped cells. That ECFC-derived colonies belonged to the endothelial lineage was confirmed by staining with anti-CD31, anti-CD105, anti-CD144, anti-CD146, antivon Willebrand factor, anti-CD45, and anti-CD14 monoclonal antibodies and by assessment of capillary-like network formation in the in vitro tube formation assay.

For our experiments, we have mainly used endothelial cells obtained from early-passage ECFCs (P2-4, which roughly encompasses a 15- to 18-day period) with the purpose to avoid, or maximally reduce, any potential bias due to cell differentiation. However, to make sure that the phenotype of the cells did not change throughout the experiments, in the preliminary experiments, we tested the immunophenotype of ECFCs at different passages, and we found no differences. We also tested whether functional differences occurred when early (P2) and late (P6)passage ECFCs were used by testing the in vitro capacity of capillary network formation in a Cultrex assay and found no differences between early- and late-passage ECFC-derived cells (data not shown).

Electrophysiological recordings were performed using a patch-clamp setup (Axopatch 200B; Axon Instruments) coupled to an inverted microscope (Nikon Eclipse Ti). ECFCs were measured in whole-cell configuration with freshly pulled glass pipettes (3 to 6 M), filled with the following intracellular solution: 12 mM KCl, 125 mM K-gluconate, 1 mM MgCl2, 0.1 mM CaCl2, 10 mM EGTA, 10 mM Hepes, and 10 mM ATP (adenosine 5-triphosphate)Na2. The extracellular solution contained the following: 135 mM NaCl, 5.4 mM KCl, 5 mM Hepes, 10 mM glucose, 1.8 mM CaCl2, 1 mM MgCl2. Only single cells were selected for recordings. Acquisition was performed with the pCLAMP 10 software (Axon Instruments). Membrane currents were low pass filtered at 2 kHz and digitized with a sampling rate of 10 kHz (Digidata 1440 A; Molecular Devices). Data were analyzed with Clampfit (Axon Instruments) and Origin 8.0 (OriginLab Corporation).

For optical excitation of the polymer, a homemade petri cell culture illuminator, compatible with the use within the cell incubator, was designed and implemented. Its design included a black spacer made by fused filament fabrication, both to minimize overheating effects in the extracellular bath and to avoid unwanted light scattering/diffusion effects and cross-talk between different specimens. Optical excitation was provided by a green LED system, whose duty cycle, repetition rate, and intensity were set through a custom-made control circuit, comprising a microcontroller, a digital-to-analog converter, and an analog LED driver. The driver was connected to five green LEDs (SMB1N-525V-02; Roithner LaserTechnik GmbH, Vienna, Austria), with maximum emission wavelength at 525 nm, each carrying a collimator lens reducing the emission angle to 22. This way, up to five 3.5-cm petri dishes can be simultaneously treated with a homogeneous photoexcitation density of 40 mW/cm2. The long-term optical excitation protocol adopted for cell fate modulation consists of 30-ms-long pulses, followed by 70-ms-long dark conditions, continuously repeated for a minimum of 4 up to 36 hours in the case of tubulogenesis and proliferation assays, respectively.

Growth dynamics were evaluated by plating a total of 5 103 ECFC-derived cells into 10-mm fibronectin-treated cloning cylinders (5 104/cm2) in the presence of EGM-2 MV medium to facilitate the adhesion. After 12 hours, the medium was switched to EBM-2 supplemented with 2% fetal calf serum. For the pharmacological treatment, one of compounds was added to the medium: BAPTA (30 M), CPZ (10 M), RN-1734 (20 M), or RR (10 M). Cultures were incubated at 37C (in 5% CO2 and humidified atmosphere), and cell growth was assessed after 36 hours since the beginning of the long-term illumination protocol. At this point, cells were recovered by trypsinization from all the dishes, and the cell number was assessed by counting in a hemocytometer. Preliminary experiments showed no unspecific or toxic effect for each agent when used at these concentrations. Each assay was repeated in triplicate.

ECFC-derived cells from early-passage (P2 to P4) cultures were obtained by trypsinization and resuspended in EBM-2 supplemented with 2% FBS. EPC-derived cells (10 103) per well were plated in Cultrex basement membrane extract (Trevigen Inc., Gaithersburg, MD, USA) 10-mm fibronectin-treated cloning cylinders. Plates were then incubated at 37C, 5% CO2, and capillary network formation was assessed starting from 4 to 24 hours later. At least three different sets of cultures were performed every experimental point. Quantification of tubular structures was performed after 8 hours of incubation by measuring the total length of structures per field with the aid of the ImageJ software (National Institutes of Health, USA; http://rsbweb.nih.gov/ij/). To evaluate the role of TRPV1, the same protocol was repeated in the presence of the following drugs: BAPTA (30 M), CPZ (10 M), RN-1734 (20 M), or RR (10 M).

H2DCF-DA (Sigma-Aldrich) was used for the intracellular detection of ROS. ECFCs were seeded onto polymer and control substrates and subjected to the same photoexcitation protocol used for the in vitro tube formation assay. Immediately after the end of the protocol, cell cultures were incubated with the ROS probe for 30 min. After careful washout of the excess probe from the extracellular medium, the fluorescence of the probe was recorded (excitation/emission wavelengths, 490/520 nm; integration time, 70 ms for H2DCF-DA) with an inverted microscope (Nikon Eclipse Ti) equipped with an Analog-WDM Camera (CoolSNAP MYO, Teledyne Photometrics). To minimize the effects of the spectral overlap between the polymer absorption and emission spectra, and the probe emission, samples were turned upside down by using a homemade chamber with a 500-m-thick channel filled with extracellular medium. Variation of fluorescence intensity was evaluated over regions of interest covering single-cell areas, and reported values represent the average over multiple cells. See figure captions for additional details about statistical analysis. Image processing was carried out with ImageJ and subsequently analyzed with Origin 8.0.

Two sets of P3HT thin films (n = 12) were prepared as described above. The optical absorbance, the emission, and the Raman spectrum were measured immediately after fabrication. Then, all samples were exposed to ECFC growth medium (EBM-2 supplemented with 2% FBS) and incubated at 37C, 5% CO2 for 24 hours. The first set was taken in dark conditions (n = 6), and the second one was treated with the same optical excitation protocol used in the tubulogenesis assays (n = 6). After incubation, absorption, emission, and Raman spectrum were measured again in the same conditions as before. Absorption spectra were recorded by using a spectrophotometer (PerkinElmer Lambda 1040) in transmission mode. Photoluminescence spectra were acquired by using a Jobin-Yvon spectrofluorometer; the excitation wavelength was set at the polymer absorption peak wavelength (530 nm). Resonant Raman spectra were recorded by using visible light excitation at 532 nm (HORIBA Jobin-Yvon HR800 micro-Raman spectrometer system). Laser power intensity on the sample was kept at values lower than 0.03 mW to avoid laser-induced sample degradation. Spectra were typically recorded in the region 600 to 2000 cm1 and were calibrated against the 520.5 cm1 line of an internal silicon wafer. The signal-to-noise ratio was enhanced by repeated acquisitions (100). The measurements were conducted at room temperature (RT), and the resulting spectral resolution was 0.4 cm1.

To examine NF-B p65 subunit translocation into the nucleus in the individual ECFCs, the coverslips were fixed with 4% formaldehyde in PBS (20 min at RT) and permeabilized with 0.1% Triton X-100 in PBS (7 min at RT). Primary rabbit polyclonal anti-p65 antibody (Santa Cruz Biotechnology, catalog no. Sc-372) was applied at a final dilution of 1:100 for 1 hour at 37C in a humidified chamber. After three washes with PBS, secondary chicken anti-rabbit Alexa(488)-conjugated antibody (1:200; Invitrogen, catalog no. A-21441) was applied for 1 hour at RT. After washing (three times in PBS), nuclei were counterstained with 4,6-diamidino-2-phenylindole, dihydrochloride (DAPI; 1:5000 dilution in PBS; 20 min at RT; Invitrogen, catalog no. D1306). Last, the coverslips with cells were mounted on microscope glass slides using Fluoroshield mount medium (Sigma, catalog no. F6182). Fluorescence images were taken with the same fluorescence microscope used for the electrophysiology experiments, using standard DAPI and fluorescein isothiocyanate filters set for the acquisition of DAPI and Alexa(488) fluorescence emission, respectively.

Cells were lysed in 0.5 ml of TRI Reagent (Sigma, catalog no. T9424), and total RNA was extracted according to the manufacturers protocol. One microgram of total RNA was retrotranscribed using SensiFAST cDNA Synthesis Kit (Bioline, London, UK, catalog no. BIO-65054). Real-time polymerase chain reaction (PCR) was performed using iTaq qPCR master mix according to the manufacturers instructions (Bio-Rad, Segrate, Italy, catalog no. 1725124) on a SFX96 Real-Time System (Bio-Rad). As a control, S18 ribosomal subunit was used, whose expression did not change across the conditions. For each gene, Ct was calculated by using the formula Ct = 2^(Ct(gene) Ct(S18)). The data are expressed as a percentage variation between P3HT light and glass light conditions and P3HT dark and glass dark samples, respectively. Sequences of oligonucleotide primers are listed in table S1.

The significance of differences was evaluated with unpaired Students t test or one-way analysis of variance (ANOVA) coupled with Tukey or Dunnetts post hoc test, as appropriate. Data are represented as means standard error of the mean (SEM). P < 0.05 was considered statistically significant. Statistical analysis was performed using the GraphPad Prism 7 software (GraphPad Software Inc., La Jolla, CA).

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/9/eaav4620/DC1

Fig. S1. Local and global evaluation of the extracellular bath temperature.

Fig. S2. TRPV1 is endogenously expressed in ECFCs, and it is efficiently activated by polymer photostimulation.

Fig. S3. Current clamp measurements in HEK-293 cells.

Fig. S4. Pharmacological study on ECFCs seeded on polymer substrates in the darkEvaluation of effect on tubulogenesis.

Fig. S5. Polymer photostability.

Fig. S6. p65 NF-B nuclear translocation is unaltered in ECFCs seeded on glass subjected to light-induced photostimulation.

Fig. S7. mRNA levels of proangiogenic genes downstream of NF-B signaling.

Table S1. List of oligonucleotide primers used for real-time PCR.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: We gratefully thank I. Abdel Aziz for the characterization of the homemade petri cell culture illuminator used for long-term optical excitation and P. Falvo for the constructive criticism of the manuscript and the helpful scientific discussions. Funding: This work was jointly supported by the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation program LINCE, grant agreement no. 803621 (M.R.A.), the EU Horizon 2020 FETOPEN-2018-2020 Programme LION-HEARTED, grant agreement no. 828984 (F.L., F.M., and M.R.A.), the Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Program (20182022)Department of Biology and Biotechnology L. Spallanzani, University of Pavia (F.M.), and Fondo Ricerca Giovani from the University of Pavia (F.M.). Author contributions: F.L., F.M., and M.R.A. planned the experiments. F.L. carried out the experimental measurements (electrophysiology, short- and long-term photoexcitation, evaluation of effects on proliferation, tubulogenesis, and ROS production). V.R. provided the ECFC models, took care of the cell cultures, and contributed to the tubulogenesis and proliferation experiments. G.T. prepared the polymer samples. A.D. designed, realized, and optimized the experimental setup for the long-term photoexcitation. L.T. and D.L. carried out the immunofluorescence and real-time PCR assays. P.C. contributed to the methodological discussion about gene expression. F.L. and M.R.A. wrote the main manuscript, with help from F.M. All authors contributed to the data interpretation and approved the final manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Conjugated polymers optically regulate the fate of endothelial colony-forming cells - Science Advances

Amniotic Fluid Stem Cell Therapy Market to Rear Excessive Growth During 2018 2026 – Herald Space

Stem cells are biological cells which have the ability to distinguish into specialized cells, which are capable of cell division through mitosis. Amniotic fluid stem cells are a collective mixture of stem cells obtained from amniotic tissues and fluid. Amniotic fluid is clear, slightly yellowish liquid which surrounds the fetus during pregnancy and is discarded as medical waste during caesarean section deliveries. Amniotic fluid is a source of valuable biological material which includes stem cells which can be potentially used in cell therapy and regenerative therapies. Amniotic fluid stem cells can be developed into a different type of tissues such as cartilage, skin, cardiac nerves, bone, and muscles. Amniotic fluid stem cells are able to find the damaged joint caused by rheumatoid arthritis and differentiate tissues which are damaged. Medical conditions where no drug is able to lessen the symptoms and begin the healing process are the major target for amniotic fluid stem cell therapy. Amniotic fluid stem cells therapy is a solution to those patients who do not want to undergo surgery. Amniotic fluid has a high concentration of stem cells, cytokines, proteins and other important components. Amniotic fluid stem cell therapy is safe and effective treatment which contain growth factor helps to stimulate tissue growth, naturally reduce inflammation. Amniotic fluid also contains hyaluronic acid which acts as a lubricant and promotes cartilage growth.

With increasing technological advancement in the healthcare, amniotic fluid stem cell therapy has more advantage over the other therapy. Amniotic fluid stem cell therapy eliminates the chances of surgery and organs are regenerated, without causing any damage. These are some of the factors driving the growth of amniotic fluid stem cell therapy market over the forecast period. Increasing prevalence of chronic diseases which can be treated with the amniotic fluid stem cell therapy propel the market growth for amniotic fluid stem cell therapy, globally. Increasing funding by the government in research and development of stem cell therapy may drive the amniotic fluid stem cell therapy market growth. But, high procedure cost, difficulties in collecting the amniotic fluid and lack of reimbursement policies hinder the growth of amniotic fluid stem cell therapy market.

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The global amniotic fluid stem cell therapy market is segmented on basis of treatment, application, end user and geography: Segmentation by Treatment Allogeneic Amniotic Fluid stem cell therapy Autologous Amniotic Fluid stem cell therapy Segmentation by Application Regenerative medicines Skin Orthopedics Oncology Fetal tissue reconstruction Kidney regeneration Regeneration of neural tissue Cardiac regeneration Lung epithelial regeneration Others Drug research and development Segmentation by End User Hospital Ambulatory Surgical Centers Specialty Clinics Academic and Research Institutes Segmentation by Geography North America Latin America Europe Asia-Pacific Excluding China China Middle East & Africa

Rapid technological advancement in healthcare, and favorable results of the amniotic fluid stem cells therapy will increase the market for amniotic fluid stem cell therapy over the forecast period. Increasing public-private investment for stem cells in managing disease and improving healthcare infrastructure are expected to propel the growth of the amniotic fluid stem cell therapy market.

However, on the basis of geography, global Amniotic Fluid Stem Cell Therapy Market is segmented into six key regions viz. North America, Latin America, Europe, Asia Pacific Excluding China, China and Middle East & Africa. North America captured the largest shares in global Amniotic Fluid Stem Cell Therapy Market and is projected to continue over the forecast period owing to technological advancement in the healthcare and growing awareness among the population towards the new research and development in the stem cell therapy. Europe is expected to account for the second largest revenue share in the amniotic fluid stem cell therapy market. The Asia Pacific is anticipated to have rapid growth in near future owing to increasing healthcare set up and improving healthcare expenditure. Latin America and the Middle East and Africa account for slow growth in the market of amniotic fluid stem cell therapy due to lack of medical facilities and technical knowledge.

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Some of the key players operating in global amniotic fluid stem cell therapy market are Stem Shot, Provia Laboratories LLC, Thermo Fisher Scientific Inc. Mesoblast Ltd., Roslin Cells, Regeneus Ltd. etc. among others.

The report covers exhaustive analysis on: Amniotic Fluid Stem Cell Therapy Market Segments Amniotic Fluid Stem Cell Therapy Market Dynamics Historical Actual Market Size, 2012 2016 Amniotic Fluid Stem Cell Therapy Market Size & Forecast 2016 to 2024 Amniotic Fluid Stem Cell Therapy Market Current Trends/Issues/Challenges Competition & Companies involved Amniotic Fluid Stem Cell Therapy Market Drivers and Restraints

Regional analysis includes North America Latin America Europe Asia Pacific Excluding China China The Middle East & Africa

Report Highlights: Shifting Industry dynamics In-depth market segmentation Historical, current and projected industry size Recent industry trends Key Competition landscape Strategies of key players and product offerings Potential and niche segments/regions exhibiting promising growth A neutral perspective towards market performance

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Amniotic Fluid Stem Cell Therapy Market to Rear Excessive Growth During 2018 2026 - Herald Space

Fabry Heart Cells Grown in Lab Dish Give Hints to Cardiac Complications – Fabry Disease News

Heart cells derived from patients stem cells and grown in a lab dish can reveal important clues about the development of heart ailments associated with Fabry disease.

The study, A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology, was published in Stem Cell Reports.

Fabry is a rare genetic disorder caused by mutations in the GLA gene. Located on the X chromosome, the gene provides instructions for the production of an enzyme called alpha-galactosidase A (alpha-GAL A).

These mutations typically affect the activity of alpha-GAL A, leading to the accumulation of a type of fat called globotriaosylceramide (GL-3) in different tissues and organs, including the heart, kidneys and nervous system, gradually compromising their normal function.

For this reason, most Fabry patients develop heart disease over the course of their lives, which may progress to heart failure, the most common cause of death among people living with the disorder.

A major obstacle for advancing therapy for patients with [Fabry disease] is the knowledge gap between the direct molecular consequences of alpha-GAL A deficiency in CMs [cardiomyocytes, or heart cells] and the cascade of events driving disease in the heart; the inaccessibility of CMs from patients precludes adequate investigation of these events, especially at early stages, the investigators wrote.

In a previous study, researchers describe the generation of induced pluripotent stem cells (iPSCs) from Fabry patients carrying nonsense mutations in the GLA gene. This gave them the possibility, for the first time, to study the impact of alpha-GAL A deficiency on heart cells derived from patients iPSCs grown in a lab dish.

(iPSCs are fully matured cells that are reprogrammed back to a stem cell state, where they are able to grow into any type of cell. A nonsense mutation is a mutation in which the alteration of a single nucleotide (the building blocks of DNA) makes proteins shorter.)

Investigators from Sanofi, in collaboration with researchers at the University of Manchester, further investigated the properties of heart cells derived from patients iPSCs. Their aim was to discover more clues about the molecular mechanisms involved in the development of heart disease linked to Fabry.

Functional and structural characterization experiments revealed that heart cells from Fabry patients had higher levels of GL-3, and showed a series of abnormalities in the way they responded to electrical stimuli and in how they regulated their calcium usage, compared to heart cells from healthy people serving as controls. Calcium is essential to coordinate the hearts function by contributing to the electrical signals involved in heart muscle contraction.

When researchers analyzed the protein contents of heart cells grown in a lab dish, they found these cells produced more than 5,500 different proteins. This analysis also showed that compared to controls, heart cells from Fabry patients produced large amounts of lysosomal membrane protein 2 (LIMP-2) and heat shock-related 70 kDa protein 2 (HSPA2/HSP70-2).

(LIMP-2 is a protein normally found on the membrane of lysosomes small structures within cells that accumulate, digest, and recycle materials that regulates their transport within cells; HSPA2/HSP70-2 is a protein involved in cellular quality control, participating in the folding of other proteins and targeting abnormal proteins for degradation.)

Heart cells from Fabry patients released high amounts of cathepsin F, a protein that helps breakdown materials being transported inside lysosomes, as well as HSPA2/HSP70-2. As expected, when researchers corrected the genetic mutation associated with Fabry in heart cells derived from patients iPSCs, all these defects were reversed.

To confirm the validity of these proteins as Fabry biomarkers, researchers then forced healthy heart cells to produce high amounts of LIMP-2. They discovered this also triggered the release of large amounts of cathepsin F and HSPA2/HSP70-2, resulting in a massive accumulation of vacuoles (enclosed compartments filled with water and other substances) inside cells.

In summary, our study has shown the power of the iPSC model to reveal early functional changes and the development of a distinctive biomarker expression profile in [Fabry disease] CMs. These biomarkers may be of utility in drug screening and in elucidating the earliest pathological events and cascades in [Fabry disease] cells. Quantification in patient plasma and urine samples will be an important next step toward validating their relevance in patients, the researchers wrote.

A better understanding of these mechanisms will no doubt accelerate the development of more effective and increasingly personalized therapies for patients, they added.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

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Fabry Heart Cells Grown in Lab Dish Give Hints to Cardiac Complications - Fabry Disease News

AI uncovers genes linked to heart failure – FierceBiotech

Artificial intelligence has been embraced for its ability to offer insight from big data. By applying the technology to genetics, a research team led by Queen Mary University of London has found clues that they say could aid the development of new drugs for heart failure and identify people at risk of the disease.

Based on an AI analysis of heart MRI images from 17,000 volunteers in UK Biobank, the researchers linked genetic factors to 22% to 39% of abnormalities in the size and function of the hearts left ventricle, which pumps blood into the aorta. They published the findings in the journal Circulation.

The team identified or confirmed 14 regions in the human genome that play a part in determining the size and function of the left ventricle, becausethey contain genes that regulate the early development of heart chambers and the contraction of heart muscle. Enlargement of left ventricle is a condition that can hamper the heart muscles ability to contract and pump blood, putting the patient at high risk of heart attack.

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This study has shown that several genes known to be important in heart failure also appear to regulate the heart size and function in healthy people, said study co-author Steffen Petersen of Queen Mary in a statement. That understanding of the genetic basis of heart structure and function in the general population improves our knowledge of how heart failure evolves.

RELATED:Bayer teams up with AI firm Sensyne Health to mine NHS data for its heart disease pipeline

There is a growing interest in using AI to gain insights into cardiovascular disease. Bayer recently partnered up with Sensyne Health, which uses AI to mine patient data from the U.K. National Health Service, including genomic sequencing data and real-world evidence, to help design clinical studies and accelerate drug discovery.

Many research teams having been looking at different ways to treat heart disease, including using immune therapies and regenerative approaches. Scientists at the University of Pennsylvania, for example,developed genetically modified T cells to attack and remove cardiac fibroblasts, which can lead to cardiac fibrosis. Vanderbilt University researchers identified Roches SYN0012, originally designed to treat rheumatoid arthritis, as a promising candidate that could dampen inflammation of heart tissue after a heart attack. Such inflammation can progress to acute episodes andchronic heart failure.

To help repair damaged cardiac tissue after a heart attack, scientists at the University of Cambridge in the United Kingdom and the University of Washington combined two types of cells derived from human stem cellsheart muscle cells and supportive epicardial cells that help the muscle cells live longer. A team at the the Morgridge Institute for Research previously added a drug called RepSox to stem cells to build better smooth muscle cells that can grow into functional arterial cells.

The Queen Mary researchers believe the 14 regions of the genome they fingered in their new study could be just the beginning of a larger story about genes and heart disease. Our academic and commercial partners are further developing these AI algorithms to analyze other aspects of cardiac structure and function,lead researcher Nay Aung said in the statement.

Aung and colleagues argue the genetic markers theyve already uncovered could help identify those at high risk of developing heart disease or open up new avenues for targeted treatments. The genetic risk scores established from this study could be tested in future studies to create an integrated and personalized risk assessment tool for heart failure, Aung said.

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AI uncovers genes linked to heart failure - FierceBiotech

How nanotechnology is sizing up healthcare, beauty and conservation – The Sociable

All living organisms function under specific conditions, the so-called laws of nature. But with the expansion of scientific knowledge in the past centuries, humans havent always just been helplessly swayed by the powers of nature.

While far from controlling nature, we have invented substances and came up with strategies that allow us to stretch the boundaries of science, from altering cell processes to becoming fully immune to diseases.

One of the most promising innovations of our times nanotechnology is taking it even further. Sometimes nicknamed the next industrial revolution, it pervades virtually every field from manufacturing to the food and drink industry.

By operating on the atomic and molecular scale, nanotechnology carries out the most precise interventions. What new possibilities does it bring to industries dealing with biology?

In 2018, global healthcare nanotechnology reached $160 billion and this number is likely to grow to over $300 billion by the end of 2025. Theres no wonder why healthcare is the true harvest field of nanotechnology with diverse opportunities, mostly in diagnostics, treatment, and prevention of diseases itself.

Experts have developed nanosized diagnostic devices that can be deployed throughout the human body to monitor levels of toxins or other substances. This allows for constant and real-time monitoring of an individual on a very detailed level something that was hardly imaginable just a few years ago.

Read More:Challenges in achieving precision medicine, personalized healthcare

And whats more! due to their size, these tiny sensors can enter spaces that are normally difficult to examine, including the brain.

Regarding treatment, there have been experiments with nanosized robots that can travel through bodily fluids. They can work to deliver active substances in a highly effective way.

Likewise, they could bring implants that destroy old cells and inject healing substances to promote the growth of new ones or the recovery of existing ones.

In this respect. In fact, researchers at North Carolina State University are developing a method to deliver cardiac stem cells to damaged heart tissue.

This highly-targeted approach also means a revolution in cancer treatment as we know it: nanotechnology could eliminate the adversary side effects of the conventional methods that affect the whole system.

Read More:Doctors will navigate this passive pill cam like they were playing Xbox

And with closer oversight and enhanced possibilities for direct intervention, cancerous cells can be destroyed even before a major breakout occurs.

Scientists at the Worcester Polytechnic Institute are working on such non-invasive preventive strategies. They have developed a chip made of carbon nanotubes that can capture circulating tumor cells of all sizes.

These can be analyzed easily to help identify any early-stage tumors and monitor treatment progress.

Nanotechnology has also seen a big boom in the cosmetics industry. In recent years, we have seen a rise in the usage of various nano-substances, including peptides, proteomics, stem cells, and epigenetics. These could directly intervene against the sources of any dermatological phenomenon, be it wrinkles, pigment spots, or acne.

The potential is immense, which is demonstrated by the industrys rising investment and the fact that major cosmetic producers, including LOral, P&G, Dior, and Johnson & Johnson, publish several nanotechnology-related patents every year.

LOral specifically designated a web page to nanoparticles to educate their consumers about the power of these substances in many aspects; from intensifying the shade of mascara to providing a matte finish effect on the skin.

The uses are truly diverse. For example, we can find the adoption of nanoemulsions that encapsulate active ingredients to be carried deeper into hair shafts, or nanosilvers and nanogolds that are known for their antibacterial effects and are used in deodorant or toothpaste.

Nanotechnology is practically used in all everyday products, including moisturizers, haircare, or sunscreens.

In fact, the usage of nanoparticles in sunscreens has perhaps earned the most attention. These SPF creams contain zinc oxide and titanium dioxide as their main compounds. Such products can reflect UV rays, in contrast to the traditional chemical sunscreens that absorb the rays.

Thats why nano-powered sunscreens appear transparent, instead of leaving a white layer on the skin. Yet, this method has been associated with safety concerns, arising from the risk of the particles penetrating tissue and entering the human organism.

While there is still research to be done, an Australian study from last year disproved this notion and asserted that nano-powered sunscreens are unlikely to be harmful.

But its not just healthcare and beauty. Nanotechnology also brings opportunities to conservation and preservation. By being able to disrupt biological processes at the most detailed level, scientists are working to delay wilting and enhance desired processes, such as fostering an environment unfriendly to bacteria.

Specifically, there has been a lot of progress done in the field of food storage and preservation. For example, the encapsulation of nutraceuticals through nanotechnology is a step towards greater food safety and bioavailability, allowing us to benefit from food to its full nutritional potential.

However, similar applications could boost a plethora of other industries, including design and art, education, and science. Laboratories could find easier ways to preserve biological samples, while impressive natural artworks could be exhibited in museums for decades, bringing awe to many generations.

One of the innovations already being put to practice is the NanoFreeze technology, which can directly battle the sources of flower decay. This preservation strategy relies on a uniquely set up freezing process that can halt decomposition.

It kills present microorganisms, stops enzymatic reactions, and establishes a protected environment that prevents the occurrence of parasites. This way, NanoFreeze technology succeeds in maintaining the bloom looking fresh even years after it was cut off, bringing unprecedented possibilities to the floriculture industry and beyond.

From live-saving innovations to more mundane consumer upgrades, nanotechnology presents many opportunities for the future.

While predicted to grow significantly in the upcoming years, its crucial to understand that the innovation still hasnt reached its peak and is yet to experience its full bloom.

Disclosure: This article is brought to you by a client of an Espacio portfolio company

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How nanotechnology is sizing up healthcare, beauty and conservation - The Sociable

Hesperos Human-on-a-Chip Technology Awarded First Phase of $3.8 Million Milestone-based NIH Grant to Study Opiate Overdoses in Collaboration With UCF…

ORLANDO, Fla.--(BUSINESS WIRE)--

- Grant is part of the Helping to End Addiction Long-Term Initiative (NIH HEAL Initiative) launched in 2018 -

Hesperos, Inc., (www.hesperosinc.com) announced today the University of Central Florida (UCF) and Hesperos have received the first phase of a $3.8 million milestone-based National Institutes of Health (NIH) grant for research involving the companys human-on-a-chip system. The goal of the research is to better understand how overdosing on opiates works, their impact on multiple organs and the effect of drugs used to treat those overdose episodes including their potential toxicity to organs. James Hickman, Ph.D., Chief Scientist at Hesperos and Professor at UCF, is the principal investigator for the research.

Hesperos, Inc., (www.hesperosinc.com) announced today the University of Central Florida (UCF) received the first phase of a $3.8 million milestone-based National Institutes of Health (NIH) grant for research involving the companys human-on-a-chip system.

"We are grateful to have funding to support research in an area that represents such a large and growing need," said Dr. Hickman. "Our interconnected human-on-a-chip system provides a non-invasive way to emulate the response of compounds among all 'organ' compartments, and to concurrently predict potential toxicity and efficacy of drugs, including opioids and opioid antagonists such as Narcan."

The funding comes from the NIHs Helping to End Addiction Long-term Initiative, or the NIH HEAL Initiative. The initiative aims to improve treatments for chronic pain, curb the rates of opioid use disorder and overdose and achieve long-term recovery from opioid addiction. The National Institutes of Health launched the Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, in April 2018 to improve prevention and treatment strategies for opioid misuse and addiction and enhance pain management. More information about the grants awarded by the NIH HEAL Initiative can be found here.

Its clear that a multi-pronged scientific approach is needed to reduce the risks of opioids, accelerate development of effective non-opioid therapies for pain and provide more flexible and effective options for treating addiction to opioids, said NIH Director Francis S. Collins, M.D., Ph.D., who launched the initiative in early 2018. This unprecedented investment in the NIH HEAL Initiative demonstrates the commitment to reversing this devastating crisis.

Under this program, Hesperos will build overdose models in a multi-organ system and evaluate the acute and chronic effects of overdose treatments, such as Narcan, on overdose recovery and efficacy. The research will provide insight into the impact of both opiate overdoses and treatment drugs on the kidneys, heart, muscles and liver, as well as explore how these drugs impact the part of the brain that controls breathing to reproduce overdose conditions.

Hesperos seeks to radically change established practice in drug discovery and testing by bypassing animal experiments and extensive clinical trials to provide treatments for diseases and clinical conditions such as overdose. Dr. Hickman developed the human-on-a-chip system at UCF in collaboration with Michael Shuler, President and CEO at Hesperos and Professor Emeritus, Cornell University. UCF licensed the technology to Hesperos, which was co-founded by Dr. Hickman and Dr. Shuler.

Over the past few years we have formed multiple collaborations with companies and nonprofit organizations seeking more efficient and effective alternatives to preclinical evaluation of drugs or toxicity tests on chemicals without lengthy, expensive animal studies, Dr. Shuler said. We recently published results in Nature Scientific Reports and Science Translational Medicine supporting the ability of our system to truly revolutionize the drug discovery process.

About Hesperos:

Hesperos, Inc. is a leader in efforts to characterize an individuals biology with human-on-a-chip microfluidic systems. Founders Michael L. Shuler and James J. Hickman have been at the forefront of every major scientific discovery in this realm, from individual organ-on-a-chip constructs to fully functional, interconnected multi-organ systems. With a mission to revolutionize toxicology testing as well as efficacy evaluation for drug discovery, the company has created pumpless platforms with serum-free cellular mediums that allow multi-organ system communication and integrated computational PKPD modeling of live physiological responses utilizing functional readouts from neurons, cardiac, muscle, barrier tissues and neuromuscular junctions as well as responses from liver, pancreas and barrier tissues. Created from human stem cells, the fully human systems are the first in vitro solutions that accurately utilize in vitro systems to predict in vivo functions without the use of animal models. More information is available at http://www.hesperosinc.com

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Hesperos Human-on-a-Chip Technology Awarded First Phase of $3.8 Million Milestone-based NIH Grant to Study Opiate Overdoses in Collaboration With UCF...

Cairo heart center to be inaugurated January: Magdi Yacoub – Egypttoday

CAIRO 22 September 2019: Renowned Professor of Cardiothoracic surgery Magdi Yacoub said that the foundation stone of a heart center in Cairo will be laid soon. The center will provide cardiac care.

In an interview with Egypt Today, the Egyptian-British cardiothoracic surgeonsaid that an inauguration ceremony of the Cairo center will beheldin January 2020, and will beattended by a large number of parliamentarians, senior doctors and statesmen to support the center and urge Egyptians to donate.

The MagdiYacoub Global Heart Foundation launched a campaign in May to raise fund for the new center.

A set of remarkable scientists and public figures took part in the campaign such as Professor MagdyIshak, and Egyptian Ambassador to the United States Yasser Reda, among others.

The MagdiYacoub Global Heart Foundation supports Aswan heart centre in Upper Egypt and is raising funds for the future MagdiYacoubglobal heart centre in Cairo.

Besides providing urgently needed cardiac care, the centers impact the region and continent by advancing scientific understanding through research and building human health capacities with training programs.

The new center will cost an estimate of $150 million and will include 300 beds, hence expected to upgrade network care capacity from 33,000 to 140,000 outpatients and from 4,000 to 17,000 inpatients annually.

Moreover, the training capacity will grow from 550 to over 2300, dramatically increasing the sectors workforce.

Yacoub was among the first three surgeons to perform an open heart surgery in Nigeria in 1974. In 1986, he was part of the team that developed the techniques of the heart-lung transplantation at the National Heart and Lung Institute.

He also led a British research team at Harefield hospital in 2007, aiming to grow a part of the human heart using stem cells. These efforts were all exerted in order to overcome the shortage of heart transplant donations.

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Cairo heart center to be inaugurated January: Magdi Yacoub - Egypttoday

Autologous Stem Cell Based Therapies Market Report with Depth Analysis 2019 | Regeneus, Mesoblast – Tech Platform

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If you are involved in the Autologous Stem Cell Based Therapies industry or intend to be, then this study will provide you comprehensive outlook. Its vital you keep your market knowledge up to date segmented by Neurodegenerative Disorders, Autoimmune Diseases & Cardiovascular Diseases, , Embryonic Stem Cell, Resident Cardiac Stem Cells & Umbilical Cord Blood Stem Cells and major players. If you have a different set of players/manufacturers according to geography or needs regional or country segmented reports we can provide customization according to your requirement.

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The report provides a basic overview of the Autologous Stem Cell Based Therapies industry including definitions, classifications, applications and industry chain structure. And development policies and plans are discussed as well as manufacturing processes and capital expenditures.Further it focuses on global major leading industry players with information such as company profiles, product picture and specifications, sales, market share and contact information. Whats more, the Autologous Stem Cell Based Therapies industry development trends and marketing channels are analyzed.The study is organized with the help of primary and secondary data collection including valuable information from key vendors and participants in the industry. It includes historical data from 2012 to 2017 and projected forecasts till 2022 which makes the research study a valuable resource for industry executives, marketing, sales and product managers, consultants, analysts, and other people looking for key industry related data in readily accessible documents with easy to analyze visuals, graphs and tables. The report answers future development trend of Autologous Stem Cell Based Therapies on the basis of stating current situation of the industry in 2017 to assist manufacturers and investment organization to better analyze the development course of Autologous Stem Cell Based Therapies Market.

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Autologous Stem Cell Based Therapies Market Report with Depth Analysis 2019 | Regeneus, Mesoblast - Tech Platform

Heart Disease A Closer Look at Stem Cells

Overview of current stem cell-based approaches to treat heart disease

Since heart failure after heart attacks results from death of heart muscle cells, researchers have been developing strategies to remuscularize the damaged heart wall in efforts to improve its function. Researchers are transplanting different types of stem cell and progenitor cells (see above) into patients to repair the damaged heart muscle. These strategies have mainly used either adult stem cells (found in bone marrow, fat, or the heart itself) or pluripotent (ES or iPS) cells.

Preliminary results from experiments with adult stem cells showed that they appeared to improve cardiac function even though they died shortly after transplantation. This led to the idea that these cells can release signals that can improve function without replacing the lost muscle. Clinical trials began in the early 2000s transplanting adult stem cells from the bone marrow and then from the heart. These trials demonstrated that transplanting cells into damaged hearts is feasible and generally safe for patients. However, larger trials that were randomized, blinded, and placebo-controlled, showed fewer indications of improved function. The consensus now is that adult stem cells have modest, if any, benefit to cardiac function.

Research shows that pluripotent stem cell-derived cardiomyocytes can form beating human heart muscle cells that both release the necessary signals and replace muscle lost to heart attack. Transplantation of pluripotent stem cell-derived cardiac cells have demonstrated substantial benefits to cardiac function in animal models of heart disease, from mice to monkeys. Recently, pluripotent stem cell-derived interventions were used in clinical trials for the first time. Patches of human heart muscle cells derived from the stem cells were transplanted onto the surface of failing hearts. Early results suggest that this approach is feasible and safe, but it is too early to know whether there are functional benefits.Research is ongoing to test cellular therapies to treat heart attacks by combining different types of stem cells, repeating transplantations, or improving stem cell patches. Clinical trials using these improved methods are currently targeted to begin around 2020.Unfortunately, many unscrupulous clinics are making unsubstantiated claims about the efficacy of stem cell therapies for heart failure, creating confusion about the current state of cellular approaches for heart failure. To learn more about warning signs of these unproven interventions, please visit Nine Things to Know About Stem Cell Treatments.

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Heart Disease A Closer Look at Stem Cells

Vancouver Stem Cell Treatment Centre | Stem Cells

How do Stem Cellsfunction?Stem cells have the capacity to migrate to injured tissues, a phenomenon calledhoming. This occurs by injury or disease signals that are released from the distressed cells and tissue. Once stem cells arrive,they dock on adjacent cells to commence performing their job to repair the problem.

Stem cells serve as a cell replacementwhere they change into the required cell type such as a muscle cell, bone orcartilage. This is ideal for traumaticinjuries and many orthopedic indications.

They do not express specific human leukocyte antigens (HLAs) which helpthem avoid the immune system. Stemcells dock on adjacent cells and release proteins called growth factors, cytokines and chemokines. These factors help control many aspects of the healing and repairprocess systemically.

Stem cells control the immune system and regulate inflammation which is a keymediator of disease, aging, and is ahallmark of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

They help to increase new blood vesselformation so that tissues receive proper blood flow and the correct nutrients needed to heal as in stroke, peripheral arterydisease and heart disease.

Stem cells provide trophic support forsurrounding tissues and help hostendogenous repair. This works wellwhen used for orthopedics. In case ofdiabetes, it may help the remaining beta cells in the pancreas to reproduce orfunction optimally.

As CSN research evolves, the field ofregenerative medicine and stem cells offers the greatest hope for those suffering from degenerative diseases, conditions for which there is currently no effective treatment or conditions that have failed conventional medical therapy.

Stem cell treatment is a complex process allowing us to harvest the bodys own repair mechanism to fight against degeneration, inflammation and general tissue damage. Stem cells are cells that can differentiate into other types of tissue to restore function and reduce pain.

Adult stem cells are found in abundance in adipose (fat) tissue, where more than 5million stem cells reside in every gram. These stem cells are called adult mesenchymal stem cells.

Our medical doctors extract stromal vascular fraction (SVF) from your own body to provide treatment using your very own cells. This process is calledautologous mesenchymal stem celltherapy. Our multi-specialty team deploys SVF under an institutional review board (IRB). This is an approved protocol that governs investigational work and the focus is to maintain safety of autologous use of SVF for various degenerative conditions.

How do we perform the stem cell treatment?Our procedure is very safe and completed in a single visit to our clinic. On the day of treatment, our physicians inject a localanaesthetic and harvest approximately 60 cc (2 oz.) of stromalvascular fraction (SVF) from under the skin of your flanks or abdomen. The extracted SVF is then refined in a closed system using strictCSN protocols to produce pure stromalvascular fraction (SVF). SVF containsregenerative cells including mesenchymal and hematopoietic stem cells, macrophages, endothelial cells, immune regulatory cells, and important growth factors that facilitate your stem cell activity. CSN technology allows us to isolate high numbers of viable stem cells that we can immediately deploy directly into a joint, trigger point, and/or byintravascular infusion. Specific deployment methods have been developed that are unique for each condition being treated.

During the refinement process, thesubcutaneous harvested cells andtheir connecting collagen matrix willbe separated, leaving purified free stem cells. About half of the SVF will be pure stem cells, while the remainder will be acombination of other regenerative cellsand growth factors. Before the SVF isre-injected into your body during the final part of the process we perform a qualityand quantity test which will examine the cell count and viability.

Perfecting the stem cell treatmentOur team records cell numbers and viability so that we can gain a better understanding of what constitutes a successful treatment. Although it is not yet possible to predict what number of cells that will be recovered in a harvest, it is very important that we know the total cell count and cell viability. It is only with this data that we will beginto understand why treatments are verysuccessful, only slightly successful orunsuccessful.

While vigilant about patient safety, we are also learning and sharing with the CSN data bank about which diseases respond best and which deployment methods are most effective with over 80 other clinics.

This data collection from all over the world makes the Cell Surgical Network the worlds largest regenerative medicineclinical research organization.

Network physicians have the opportunity to share their data, as well as their clinical experiences, thus helping one anotherto achieve higher levels of scientificunderstanding and optimizing medical protocols.

Injecting into thevascular system and/ora jointWe will administer the stem cell treatment with two methods:

The belief is that for many degenerative joint conditions IV and intra-articulardeployment is superior because each of these conditions have a local pathology and a central pathology. The local resident stem cell population has been working very hard to repair the damage and over the course of time these stem cells have become worn out, depleted and slowly die. This essentially causes a state of stem cell depletion. When we inject our mix of stem cells, cytokines and growth factors (known as SVF)inflammation is decreased and theregenerative process improved.

The stem cells that we have injected will then bring the level of stem cells closer to the normal level, thus restoring the natural balance and allow the body to heal itself.

Caplan et al, The MSC: An Injury Drugstore, DOI 10.1016/j .stem.2011.06.008

How long does it last?Many studies have shown the healing and regenerative ability of stem cells. Forexample, a study in World Journal of Plastic Surgery (Volume 5[2]; May 2016) followed a woman with knee arthritis. Before and after analysis of MRI images confirmed new growth of cartilage tissue. Unlike steroids, lubricants, and other injectable treatments, stem cells actually repair damaged tissue.

As published in Experimental andTherapeutic Medicine (Volume 12[2]; August 2016), numerous studies with hundreds of patients showed continuous improvement of arthritis for two years. Patients showed improvement three months after a single treatment and they continued to show improvement for two full years. This is why stem cells are often referred to as regenerative medicine.

No one can guarantee results for this or any other treatment. Outcomes will vary from patient to patient. Each potential patient must be assessed individually to determine the potential for optimum results from this regenerative therapy. To learn more about stem cell therapy, please contact us by clicking here or calling our clinic at 604-708-CELL (604-708-2355).

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Vancouver Stem Cell Treatment Centre | Stem Cells

Stem Cell Basics VII. | stemcells.nih.gov

There are many ways in which human stem cells can be used in research and the clinic. Studies of human embryonic stem cells will yield information about the complex events that occur during human development. A primary goal of this work is to identify how undifferentiated stem cells become the differentiated cells that form the tissues and organs. Scientists know that turning genes on and off is central to this process. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. A more complete understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. Predictably controlling cell proliferation and differentiation requires additional basic research on the molecular and genetic signals that regulate cell division and specialization. While recent developments with iPS cells suggest some of the specific factors that may be involved, techniques must be devised to introduce these factors safely into the cells and control the processes that are induced by these factors.

Human stem cells are currently being used to test new drugs. New medications are tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines have a long history of being used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor drugs. The availability of pluripotent stem cells would allow drug testing in a wider range of cell types. However, to screen drugs effectively, the conditions must be identical when comparing different drugs. Therefore, scientists must be able to precisely control the differentiation of stem cells into the specific cell type on which drugs will be tested. For some cell types and tissues, current knowledge of the signals controlling differentiation falls short of being able to mimic these conditions precisely to generate pure populations of differentiated cells for each drug being tested.

Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including maculardegeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

Figure 3. Strategies to repair heart muscle with adult stem cells. Click here for larger image.

2008 Terese Winslow

For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stromal cells, transplanted into a damaged heart, can have beneficial effects. Whether these cells can generate heart muscle cells or stimulate the growth of new blood vessels that repopulate the heart tissue, or help via some other mechanism is actively under investigation. For example, injected cells may accomplish repair by secreting growth factors, rather than actually incorporating into the heart. Promising results from animal studies have served as the basis for a small number of exploratory studies in humans (for discussion, see call-out box, "Can Stem Cells Mend a Broken Heart?"). Other recent studies in cell culture systems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells (Figure 3).

Cardiovascular disease (CVD), which includes hypertension, coronary heart disease, stroke, and congestive heart failure, has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic. Nearly 2,600 Americans die of CVD each day, roughly one person every 34 seconds. Given the aging of the population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes, CVD will be a significant health concern well into the 21st century.

Cardiovascular disease can deprive heart tissue of oxygen, thereby killing cardiac muscle cells (cardiomyocytes). This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells attempting to sustain cardiac output, leading to heart failure, and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is therefore a potentially new strategy to treat heart failure.

The use of embryonic and adult-derived stem cells for cardiac repair is an active area of research. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells including mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated as possible sources for regenerating damaged heart tissue. All have been explored in mouse or rat models, and some have been tested in larger animal models, such as pigs.

A few small studies have also been carried out in humans, usually in patients who are undergoing open-heart surgery. Several of these have demonstrated that stem cells that are injected into the circulation or directly into the injured heart tissue appear to improve cardiac function and/or induce the formation of new capillaries. The mechanism for this repair remains controversial, and the stem cells likely regenerate heart tissue through several pathways. However, the stem cell populations that have been tested in these experiments vary widely, as do the conditions of their purification and application. Although much more research is needed to assess the safety and improve the efficacy of this approach, these preliminary clinical experiments show how stem cells may one day be used to repair damaged heart tissue, thereby reducing the burden of cardiovascular disease.

In people who suffer from type1 diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient's own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for persons with diabetes.

To realize the promise of novel cell-based therapies for such pervasive and debilitating diseases, scientists must be able to manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation, and engraftment. The following is a list of steps in successful cell-based treatments that scientists will have to learn to control to bring such treatments to the clinic. To be useful for transplant purposes, stem cells must be reproducibly made to:

Also, to avoid the problem of immune rejection, scientists are experimenting with different research strategies to generate tissues that will not be rejected.

To summarize, stem cells offer exciting promise for future therapies, but significant technical hurdles remain that will only be overcome through years of intensive research.

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Stem Cell Basics VII. | stemcells.nih.gov

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