Archive for the ‘Cardiac Stem Cells’ Category

BROOMFIELD, Colo., April 17, 2017 /PRNewswire/ -- "Interventional orthopedics in pain medicine practice" was recently published by Elsevier as a chapter in Techniques in Regional Anesthesia and Pain Management. The chapter, authored by Regenexx founder Christopher J. Centeno, MD examines less invasive ways to treat orthopedic pain and injuries through autologous biologics, such as stem cells and platelet rich plasma (PRP), and the shift from surgical orthopedics to interventional orthopedics.

Interventional orthopedics utilizing advanced technologies, such as ultrasound and X-ray guidance, precise percutaneous injections of autologous biologics, and bone marrow concentrate, (BMC) expand nonsurgical options in the field of orthopedics. Citing the dramatic reduction in cardiac surgery rates since the adoption of the specialty interventional cardiology, the authors reveal, "We are poised on the brink of the same change in orthopedic care." The authors also state, "The field of autologous biologics has the potential to alter the playing field of orthopedic care by allowing percutaneous injections to replace the need for more invasive orthopedic surgeries."

The chapter covers three important tenets in the developing field that will allow Interventional Orthopedics to alter traditional orthopedic care in the future. First is the rapid expansion of injectates (material being injected), such as stem cells and PRP, that can help heal damaged tissue and that can effectively treat musculoskeletal tissues. Second is the precise image-guided placement of those injectates into those damaged tissues. And third is the development of new tools that will advance this regenerative-medicine technology. The chapter also highlights research that supports the use of bone marrow stem cells and the importance of education standards and organization, training, and retraining of physicians to meet these standards.

The full chapter "Interventional orthopedics in pain medicine practice" can be found online at http://www.sciencedirect.com/science/article/pii/S1084208X16300052.

Christopher J. Centeno, MD, is the CEO of Regenexx and an international expert and specialist in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedics. Dr. Centeno maintains an active research-based practice and has multiple publications listed in the US National Library of Medicine.He has also served as editor-in-chief of a medical research journal dedicated to traumatic injury and is one of the few physicians in the world with extensive experience in the culture expansion of and clinical use of adult stem cells to treat orthopedic injuries.

MEDIA CONTACT Mark Testa 155014@email4pr.com (303) 885-9630

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/regenexx-network-using-regenerative-medicine-technologies-in-interventional-orthopedics-to-treat-pain-300439851.html

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Regenexx Network Using Regenerative Medicine Technologies in Interventional Orthopedics to Treat Pain - Yahoo Finance

April 11, 2017 07:15 ET | Source: Cesca Therapeutics Inc.

RANCHO CORDOVA, Calif., April 11, 2017 (GLOBE NEWSWIRE) -- Cesca Therapeutics Inc. (Nasdaq:KOOL), a market leader in automated cell processing and point-of-care, autologous cell-based therapies, today announced that Dr. Xiaochun (Chris) Xu, Chairman and Interim Chief Executive Officer and Chairman of Boyalife Group, will present an overview of the Companys cardiovascular clinical research program at the 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair, being held April 10-12, 2017 at the Hope Hotel in Shanghai, China.

Details of the presentation are as follows:

Despite recent therapeutic and surgical advances, the effects of peripheral arterial disease, including heart attack and critical limb ischemia (CLI), remain among the worlds leading causes of morbidity and mortality and represent a rapidly escalating public health crisis, noted Dr. Xu. I look forward to presenting a review of our latest findings, including key feasibility study results and an overview of our Phase 3 Critical Limb Ischemia Rapid Stemcell Treatment (CLIRST) trial, which we believe highlight the potential of Cesca Therapeutics proprietary AutoXpress point-of-care platform to deliver autologous cell-based therapies that may represent a new paradigm in patient treatment going forward.

About the Symposium of Translational Medicine in Stem Cell Myocardial Repair

The 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair brings together more than 650 of the worlds cardiac disease thought leaders to discuss the potential of translational and regenerative medicine in treating myocardial infarction (MI) and cardiac failure. The symposium is co-sponsored by the Shanghai Society for Cell Biology, the Institute of Health Sciences, the Shanghai Cardiovascular Disease Institute, the Guangzhou Institutes of Biomedicine and Health, and the Key Laboratory of Stem Cell Biology, Shanghai.

About Cesca Therapeutics Inc.

Cesca is engaged in the research, development, and commercialization of cellular therapies and delivery systems for use in regenerative medicine. The Company is a leader in the development and manufacture of automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapeutics. Cesca is an affiliate of the Boyalife Group (http://www.boyalifegroup.com), a China-based industrial-research alliance among top research institutes for stem cell and regenerative medicine.

Forward-Looking Statement

The statements contained herein may include statements of future expectations and other forward-looking statements that are based on managements current views and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. A more complete description of risks that could cause actual events to differ from the outcomes predicted by Cesca Therapeutics' forward-looking statements is set forth under the caption "Risk Factors" in Cesca Therapeutics annual report on Form 10-K and other reports it files with the Securities and Exchange Commission from time to time, and you should consider each of those factors when evaluating the forward-looking statements.

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CESCA Therapeutics to Present at the 2017 International Symposium of Translational Medicine in Stem Cell ... - GlobeNewswire (press release)

Scientists have created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack, researchers at University of Minnesota in the US said. During a heart attack, a person loses blood flow to the heart muscle and that causes cells to die.

Our bodies can not replace those heart muscle cells so the body forms scar tissue in that area of the heart, which puts the person at risk for compromised heart function and future heart failure. Researchers used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries. This is a significant step forward in treating the No 1 cause of death in the US, said Brenda Ogle, an associate professor at the University of Minnesota.

We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years, said Ogle. Ogle said that the research is different from previous ones as the patch is modelled after a digital, three- dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells.

Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue, researchers said. We were quite surprised by how well it worked given the complexity of the heart. We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch, Ogle said.

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart. The study was published in the journal Circulation Research.

Publish date: April 16, 2017 12:57 pm| Modified date: April 16, 2017 12:57 pm

Tags: 3D-Bioprint, Brenda Ogle, cells, Heart, heart attack, heart failure, Journal Circulation Research, scientists, structural proteins, University of Minnesota

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Scientists have made a 3D-printed patch that can help heal the damaged heart tissue - Tech2 (blog)

WASHINGTON D.C: Scientists have developed a revolutionary 3D-bioprinted patch that could one day be used to repair damage to the human heart.

The patch can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack.

The researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries.

"This is a significant step forward in treating the No. 1 cause of death in the U.S.," said researcher Brenda Ogle. "We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years."

Ogle said that this research is different from previous research in that the patch is modelled after a digital, three-dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells. Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue.

"We were quite surprised by how well it worked given the complexity of the heart," Ogle noted. "We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch."

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart.

The research study is published in Circulation Research, a journal published by the American Heart Association.

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Breakthrough in cardiac health: 3D-printed patch can help mend a 'broken' heart - Economic Times

It would seem the beautiful foxglove plant has more uses than just the garden.

A novel drug screen in liver-like cells shows that cardiac glycosides, which are found in the leaves of the digitalis or foxglove plant, could reduce low-density lipoprotein (LDL) cholesterol differently than statins, potentially providing a new treatment for patients.

The foxglove plant in bloom on MUSC's campus.

These findings were reported by the Medical University of South Carolina researcher Stephen A. Duncan, D.Phil., SmartState Chair of Regenerative Medicine at MUSC, and colleagues in the April 6 issue of Cell Stem Cell.

Duncan said the glycosides were identified through a stem cell screen for compounds that could be used off-label for the treatment of high cholesterol. The nice thing about finding new uses for drugs already on the market is that they can be used relatively quickly in patients because most of the needed safety trials have already been completed.

Not everyone with high LDL cholesterol responds to statins. Statins increase levels of a cell surface receptor that removes LDL cholesterol from the bloodstream. However, statins do not work in patients with familial hypercholesterolemia (FH), who have a rare mutation in that receptor. It is an inherited disorder that leads to aggressive and premature cardiovascular disease. FH patients have very high cholesterol and can die of cardiovascular disease by their forties. The existing drugs for FH can cause fatty liver disease, and the best treatment is a liver transplant.

Duncan and his graduate student Max Cayo, who is finishing his M.D. at the Medical College of Wisconsin, developed a drug screen to identify an alternative to statins. Apolipoprotein B (apoB) is a molecule that liver cells use to make LDL. Drugs that decreased apoB could potentially lower cholesterol independently of the LDL receptor in FH patients and also in patients with other forms of high cholesterol.

FH was a perfect model for testing alternatives to statins. Yet the rarity of FH meant these liver cells were scarce. Duncans group made induced pluripotent stem cells out of skin fibroblasts taken from a single patient with FH. Stem cells continually double their numbers while in culture. This meant that a sample of converted skin cells from a single patient with FH provided a renewable source of liver-like cells that retained the mutation.

The group tested these liver-like cells with the SPECTRUM library, a collection of 2,300 pharmaceuticals, many of which have reached clinical trials. Surprisingly, all nine cardiac glycosides in the collection, some widely prescribed for heart failure, reduced apoB in liver-like cells from the patient with FH. In further tests, they also lowered apoB in human hepatocytes and in mice engineered to grow normal human livers without the FH mutation.

Next, the team combed through more than five thousand medical records of patients prescribed cardiac glycosides for heart failure who also had LDL cholesterol records. Similar drops in LDL levels were observed in these patients as in a matching group of patients prescribed statins.

This study provides the first evidence that cardiac glycosides could potentially reduce LDL cholesterol independently of the LDL receptor, where statins act, by reducing apoB.

The cardiac glycosides are always prescribed with care, as they are known to be toxic at high doses. However, they could offer inexpensive life-saving options for patients with FH. Additionally, a cardiac glycoside in a low dose could conceivably provide an added benefit to patients already taking a statin. Duncan is exploring plans for a clinical trial that would determine the correct dose in hypercholesterolemia patients.

Using patient stem cells to screen drugs that are already on the market is a great way to investigate treatments for liver diseases.

There are so few livers available for transplant, Duncan said. Having the stem cell model where we make liver cells in the culture dish opens up a possibility of using this not only to investigate a disease, but also as a way to discover drugs that could fix a disease.

This article has been republished frommaterialsprovided by theMedical University of South Carolina. Note: material may have been edited for length and content. For further information, please contact the cited source.

Excerpt from:
SPECTRUM Drug Screen Reveals Fox Gloves Can Treat High Cholesterol - Technology Networks

April 10, 2017 06:00 ET | Source: Mesoblast Limited

NEW YORK and MELBOURNE, Australia, April 10, 2017 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO) (ASX:MSB) today announced that thePhase 3 trial ofits allogeneic mesenchymal precursor cell (MPC) product candidate MPC-150-IM in patients with moderate to advanced chronic heart failure (CHF)was successful in thepre-specified interim futility analysisof the efficacy endpoint in the trial's first 270 patients. It is expected that the trial will enroll in total approximately 600 patients. After notifying the Company of the interim analysis results, thetrials Independent Data Monitoring Committee (IDMC) additionally stated that they had no safety concerns relating to MPC-150-IM and formally recommended that the trial should continue as planned.

Dr. Emerson C. Perin,Director, Research in Cardiovascular Medicine and Medical Director, Stem Cell Center at the Texas Heart Institute, and a lead investigator on the ongoing Phase 3 trial said: "It is very pleasingto see that thislarge and rigorously conducted Phase 3 trialof Mesoblast's cell therapy was successful in the pre-specified interim futility analysis for the trial's efficacy endpoint in the first 270 patients. Advancedheart failure is a very serious and life-threatening disease, and there is an urgent need to develop a safe and effective new therapy for these patients that may halt or reverse disease progression and prevent the high associated mortality.

Mesoblast Chief Executive Silviu Itescucommented: Passing this interim futility analysis for MPC-150-IM is an important milestone for Mesoblast and our cardiovascular disease program. This validates our strategy and our prioritization of this valuable program.

This ongoing double-blinded randomized (1:1) trial is currently being conducted across multiple study sites in the United States and Canada.It is evaluating MPC-150-IM in adult patients with moderate to advanced New York Heart Association (NYHA) Class II/III chronic heart failure with left ventricular systolic dysfunction. The trials primary efficacy endpoint is a comparison of recurrent non-fatal heart failure-related major adverse cardiac events (HF-MACE) in moderate to advanced CHF patients receiving either MPC-150-IM by catheter injection into the damaged left ventricular heart muscle or sham control. A Joint Frailty Model is the statistical method that evaluates multiplenon-fatal heart failure-relatedevents per patient (such as repeated hospitalizations for decompensated heart failure) while accounting for increased likelihood of a terminal cardiac event (such as death, implantation of a mechanical heart assist device or a heart transplant) for patients with multiple non-fatal heart failure events. In line with best practice for blinded Phase 3 clinical trials, the interim analysis data are only reviewed by the IDMC. Mesoblast, the United States Food and Drug Administration (FDA), and trial investigators are blinded to grouped safety and efficacy data for the ongoing trial as well as the numerical results of this interim analysis.

About Mesoblasts MPC-150-IM Cardiovascular Program MPC-150-IM is Mesoblast's lead allogeneic, cell-based product candidate for the treatment of moderate to advanced chronic heart failure (CHF) due to left ventricular systolic dysfunction.

In Phase 2 results, a single injection of MPC-150-IM into the myocardium of patients with moderate to advanced chronic heart failure prevented any HF related hospitalizations or cardiac deaths over three years of follow-up.1 Nonclinical studies showed that intramyocardial administration of MPCs in animal models of heart failure improved cardiac function and attenuated pathological ventricular remodelling. These effects were attributable, at least in part, to MPC secretion of biomolecules that stimulate reparative processes in the failing heart including new blood vessel formation, cardiac muscle cell survival, and reduction in tissue fibrosis.

MPC-150-IM is also being studied in a Phase 2b trial in 159 patients with NYHA Class IV end-stage heart failure patients in conjunction with implantation of a left ventricular assist device (LVAD).A major objective of this trial, which is being sponsored by the United States National Institutes of Health (NIH), is to assess the ability of MPC-150-IM to help wean patients from a LVAD dependent existence for survival (so-called bridge to recovery).

Additionally, the FDA recently cleared the commencement of a 24-patient trial which is being sponsored by Bostons Childrens Hospital. This study combines Mesoblast's proprietary allogeneic MPC-150-IM product with corrective heart surgery in children under the age of 5 with hypoplastic left heart syndrome.

About Chronic Heart Failure In 2016, more than 15 million patients in the seven major global pharmaceutical markets are estimated to have been diagnosed with CHF.2 Prevalence is expected to grow 46% by 2030 in the United States alone, affecting more than 8 million Americans.3 CHF is a progressive disease and is classified in relation to the severity of the symptoms experienced by the patient. The most commonly used classification system was established by the NYHA and ranges from Class I (mild) to Class IV or end stage (severe). Approximately half of people who develop heart failure die within 5 years of diagnosis.4 Patients with late NYHA Class II or Class III CHF continue to represent a significant unmet medical need despite recent advances in new therapies. CHF causes severe economic, social, and personal costs. In the United States, it is estimated that CHF results in direct costs of $60.2 billion annually when identified as a primary diagnosis and $115 billion as part of a disease milieu.5

1.Perin EC, Borow KM, Silva GV, et al. A phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failure. Circ Res. 2015; 117:576-84

2.GlobalData-PharmaPoint (2016): Heart Failure-Global Drug Forecast and Market Analysis to 2025

3.AHA Statistical Update Heart Disease and Stroke Statistics-(2017). Circulation. 2017;131:00-00. DOI: 10.1161/CIR.0000000000000485

4.Mozzafarian D, Benjamin EJ, Go AS, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics2016 update: a report from the American Heart Association. Circulation. 2016;133:e38-e360

5.A Re-Evaluation of the Costs of Heart Failure and its Implications for Allocation of Health Resources in the United States. Voigt J. Clinl.Cardiol. 37, 5, 312-321 (2014)

About Mesoblast Mesoblast Limited (Nasdaq:MESO) (ASX:MSB)is a global leader in developing innovative cell-based medicines. The Company has leveraged its proprietary technology platform, which is based on specialized cells known as mesenchymal lineage adult stem cells, to establish a broad portfolio of late-stage product candidates. Mesoblasts allogeneic, off-the-shelf cell product candidates target advanced stages of diseases with high, unmet medical needs including cardiovascular conditions, orthopedic disorders, immunologic and inflammatory disorders and oncologic/hematologic conditions.

Forward-Looking Statements This press release includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast's actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

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Successful Interim Analysis of Efficacy Endpoint in Mesoblast's Phase 3 Trial for Chronic Heart Failure - GlobeNewswire (press release)

Q. Im in doubt regarding myelodysplasia is it multipotent or pluripotent?

A. Thats a great question because it lets us talk about hematopathology (yay!) and also stem cells (which can be confusing unless someone explains some simple stuff).

What is a stem cell? First, lets talk about stem cells. The thing that makes a stem cell a stem cell, at least in my mind, is the ability to self-renew. This means that the stem cell can either divide into two daughter cells which will mature into grown up cells, or (and more commonly) it can give rise to two cells: one that will become a mature cell, and another which retains the capacity to divide again. Its called asymmetric division: instead of giving rise to two of the same cells, you get one regular cell and another stem cell (which can continue this cycle of replication for a long long time).

(Virtually) limitless replication Most cells have a limited number of times that they can divide. This is because the telomeres (little protective DNA sequences) on the end of the chromosomes get a little shorter every time the DNA replicates and eventually they are so short that they cant protect the DNA and the cell is unable to divide. Stem cells and cancer cells have an enzyme called telomerase that replenishes the telomeres, keeping them nice and long so the cell can keep on dividing. Stem cells do eventually die so technically, there are a limited number of cell divisionsbut its a really, really big number. Cancer cells, on the other hand, are often totally immortal they can just keep on dividing and dividing.

Totipotent Another cool thing about stem cells is that they can give rise to many different kinds of cells. Heres where things can get murky. There are stem cells in an embryo which are able to give rise to any of the cell types in the body: hepatocytes, epithelial cells, neurons, cardiac muscle cellseverything. This makes sense: if youre going to grow into a human, you have to have cells that give rise to all the necessary cell types. These stem cells are called totipotent or pluripotent stem cells. Theres a slight difference between the two words: totipotent means that the stem cell can give rise to any and all human tissue cells and it can even give rise to an entire functional human. The only totipotent cells in human development are the fertilized egg and the cells in the next few cell divisions.

Pluripotent After those few cell divisions, the cells become pluripotent. Pluripotent cells are similar to totipotent cells in that they can give rise to any and all human tissue cells. Theyre different, though, because they are not capable of giving rise to an entire organism. On day four of development, the tiny little embryo forms two layers: one that will become the placenta and the other that will become the baby. The cells that will become the baby can give rise to any human tissue type (obviously) but those cells alone cant give rise to the entire organism (because you cant form the baby without the placenta). Slight difference but enough to make a separate term.

Multipotent Another term you should know is multipotent. Multipotent stem cells cannot give rise to any old cell in the body they are restricted to a limited range of cell types. For example, there are multipotent stem cells in the bone marrow that can give rise to red cells, white cells and platelets. They cant give rise to hepatocytes, or any other cell type, though so they are not totipotent or pluripotent.

There are lots of multipotent stem cells in the adult human body. They reside in the bone marrow, skin, muscle, GI tract, endothelium, and mesenchymal tissues. This means that there is a nice source for replacing cells that have died or been sloughed away.

What about myelodsyplasia? So back to your question. Myelodysplasia is a hematopoietic disorder in which cells in the bone marrow grow funny (dysplasia) they might be binucleate, or not have the normal number of granules, or whatever. In addition, some cases have an increase in blasts in the bone marrow but not over 20%, or youd call it an acute leukemia. Some cases transform, eventually, into an acute myeloid leukemia; others just stay the way they are and dont become nasty.

Check out the image above, from a case of myelodysplasia. There is a bizarre, multinucleated erythroblast at 11 oclock (this is called dyserythropoiesis, or disordered red cell growth). There are also two messed-up neutrophils (dysgranulopoiesis) at 4 oclock and 10 oclock the one at 4 oclock has only two nuclear lobes, and both are hypogranular (not enough specific granulation). Theres also an increase in blasts, if this field is representative: theres one in the middle and (probably) one at 5 oclock.

This disorder (actually, its a group of disorders) involves stem cells in the bone marrow. Sometimes only one cell line is involved (red cells, say); other times all three cell lines are involved (red cells, white cells and platelets). Either way, the disorder involves a stem cell, and since the stem cells in the bone marrow are multipotent, it would be correct to say that myelodysplasia is a disorder of multipotent stem cells in the bone marrow. Its kind of redundant, though, because as far as we know, there arent any other kind of stem cells in the bone marrow! But at least you know the answer to your question now.

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Multipotent vs. pluripotent stem cells - Pathology Student

RANCHO CORDOVA, Calif., April 11, 2017 (GLOBE NEWSWIRE) -- Cesca Therapeutics Inc. (KOOL), a market leader in automated cell processing and point-of-care, autologous cell-based therapies, today announced that Dr. Xiaochun (Chris) Xu, Chairman and Interim Chief Executive Officer and Chairman of Boyalife Group, will present an overview of the Companys cardiovascular clinical research program at the 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair, being held April 10-12, 2017 at the Hope Hotel in Shanghai, China.

Details of the presentation are as follows:

Despite recent therapeutic and surgical advances, the effects of peripheral arterial disease, including heart attack and critical limb ischemia (CLI), remain among the worlds leading causes of morbidity and mortality and represent a rapidly escalating public health crisis, noted Dr. Xu. I look forward to presenting a review of our latest findings, including key feasibility study results and an overview of our Phase 3 Critical Limb Ischemia Rapid Stemcell Treatment (CLIRST) trial, which we believe highlight the potential of Cesca Therapeutics proprietary AutoXpress point-of-care platform to deliver autologous cell-based therapies that may represent a new paradigm in patient treatment going forward.

About the Symposium of Translational Medicine in Stem Cell Myocardial Repair

The 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair brings together more than 650 of the worlds cardiac disease thought leaders to discuss the potential of translational and regenerative medicine in treating myocardial infarction (MI) and cardiac failure. The symposium is co-sponsored by the Shanghai Society for Cell Biology, the Institute of Health Sciences, the Shanghai Cardiovascular Disease Institute, the Guangzhou Institutes of Biomedicine and Health, and the Key Laboratory of Stem Cell Biology, Shanghai.

About Cesca Therapeutics Inc.

Cesca is engaged in the research, development, and commercialization of cellular therapies and delivery systems for use in regenerative medicine. The Company is a leader in the development and manufacture of automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapeutics. Cesca is an affiliate of the Boyalife Group (http://www.boyalifegroup.com), a China-based industrial-research alliance among top research institutes for stem cell and regenerative medicine.

Forward-Looking Statement

The statements contained herein may include statements of future expectations and other forward-looking statements that are based on managements current views and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. A more complete description of risks that could cause actual events to differ from the outcomes predicted by Cesca Therapeutics' forward-looking statements is set forth under the caption "Risk Factors" in Cesca Therapeutics annual report on Form 10-K and other reports it files with the Securities and Exchange Commission from time to time, and you should consider each of those factors when evaluating the forward-looking statements.

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CESCA Therapeutics to Present at the 2017 International Symposium of Translational Medicine in Stem Cell ... - Yahoo Finance

TWIN FALLS Two therapists with Primary Therapy Source have recently pursued continuing education opportunities.

Physical Therapist Assistant David Fowers attended a continuing education class in Boise in March.

Functional Strength: An Updated Approach to Exercising Our Patients provided him the ability to advance his understanding of therapeutic exercise and create basic to advanced functional exercise programs. These can be customized for patients.

Teresa Prine, who has a masters degree in physical therapy, attended the Big Sky Athletic Training and Sport Medicine Conference.

The topics discussed included sudden cardiac death in athletes, the importance of eye movements in evaluation of brain injury, fracture healing, focused nutrition, stem cell procedure benefits, exertional heat illness, overuse injuries and cardiac issues in athletes.

Prine also attended the Big Sky Concussion Conference to learn about current research for targeted treatment, oculomotor measures, concussion clinical profiles, gender considerations and concussion in youth contact sports. She can be reached at Primary Therapy Source at 208-734-7333.

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Therapists receive continuing education - Twin Falls Times-News

A team of scientists from the University of California, Los Angeles has been able to synthesize an artificial thymus, a human organ that is important to the bodys immune system. An artificial thymus, they say, could produce necessary cancer-fighting T-cells for the body.

On demand.

T-cells, of course, are white blood cells which naturally fight diseases that develop in or infect the body. These T-cells are artificial, though, so they would have to be engineered to target specific forms of cancer, in order to be effective. Still, if this is manageable, then it could provide scientists and health practitioners with additional natural defensesalbeit, bionicfor attacking disease.

The thymus rests in front of the heart. It uses stem cells from the blood to make immune-boosting T-cells, which literally circulate throughout the body to specifically target things that dont belong. In this case, the thymus would create T-cells that could seek out specific cancerous growths without jeopardizing the health of existing tissue.

For the study, the Japanese researchers looked at 27 patients who had received transplants form stem cells that had been taken from their own thigh muscles. These patients showed no sign of any major complications; most patients also showed significant improvement with their symptoms.

Research team member Gay Crooks comments, We know that the key to creating a consistent and safe supply of cancer-fighting T-cells would be to control the process in a way that deactivates all T-cell receptors in the transplanted cells, except for the cancer-fighting receptors. It is important, of course, to take stem cells from the patient who needs them because the body is likely to reject any foreign stem cells (and their byproducts). Apparently, they have been at this study for more than two decades but, unfortunately, the researchers acknowledge that past attempts only showed modest results. From these results, though, they were able to devise a method for producing sheets of muscle stem cells which could then be attached to the inner layer of the sac (which encloses the heart). These stem cells will stimulate healing through the production of chemicals which encourage cardiac regeneration, though the stem cells, themselves, do not survive in the long term.

The results of this study have been published in the scientific journal Nature Methods.

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Can An Artificial Thymus, Made from Stem Cells, Pump Out Enough T-Cells To Fight Cancer? - Dispatch Tribunal

Science Daily

How cells react to injury from open-heart surgery: Research ... Science Daily Investigators have learned how cardiac muscle cells react to a certain type of injury that can be caused by open-heart surgery. The findings point to a new ... and more »

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How cells react to injury from open-heart surgery: Research ... - Science Daily

TiGenix reports 2016 full year results | P&T Community P&T Community PRESS RELEASERegulated informationinsider information TiGenix reports 2016 full year results (Conference call and webcast today at 13:00 CEST) and more »

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TiGenix reports 2016 full year results | P&T Community - P&T Community

A stem cell treatment for heart failure patients is safe and shows early signs of effectiveness, according to a study published Wednesday.

The study was conducted by Japanese researchers in 27 patients, who received transplants of stem cells taken from their own thigh muscles. There were no major complications, and most patients showed considerable improvement in their symptoms.

The study was published in the open-access Journal of the American Heart Association. Dr Yoshiki Sawa of Osaka University Graduate School of Medicine was the senior author. It can be found at j.mp/stemheart.

However, two San Diego cardiologists who do stem cell research on heart disease cautioned that similar clinical trials have shown promise over the years, only to fail at the end for various reasons. There is no approved stem cell therapy for heart failure.

So while the trial itself appears to be well-conducted, the researchers are very far from actually proving their treatment is effective, said Dr. Richard Schatz of Scripps Health and Dr. Eric Adler of UC San Diego School of Medicine.

For one thing, the trial was small, they said, and larger trials are where the most rigorous scientific evaluations are made.

These early trials have looked beneficial in the past, Adler said. When we do the larger trials, the results are more equivocal.

Adler said the signs of efficacy in this trial are modest. For example, the change in ejection fraction, a measurement of efficiency in pumping blood, rose from 27 percent to 30 percent in 15 of the 27 patients. Their heart failure was associated with a lack of blood flow, or ischemia. The remaining non-ischemic patients actually had a slight decline.

The entire field of stem cell and regenerative therapy for heart disease has been a disappointment to date, Schatz said.

Weve been at it for 20 years now, and we dont have a product or a positive (late-stage) trial, so that tells you pretty much everything you need to know, he said. Its not for lack of trying or billions of dollars invested. Its just very, very difficult.

The cardiac field has had more success with other technologies, such as cardiac stents. Schatz is the co-inventor of the first stent.

In the study, the researchers acknowledge that previous attempts had only been modestly effective. They devised a method of producing sheets of muscle stem cells and attaching them to the inner layer of the sac that encloses the heart, a layer that rests directly on the heart surface.

The stem cell sheets stimulate healing by producing chemicals that stimulate cardiac regeneration, the study said. The cells themselves dont survive in the long term, but by the time they die they have served their purpose.

Loss of function

Heart failure is a progressive disease in which the heart gradually loses its ability to pump blood. This can be triggered by a heart attack or any other cause that damages the heart muscle.

When damaged heart muscle is replaced with scar tissue, as often happens, the heart loses pumping capacity. It becomes overstressed, and its output of blood declines. This limits the patients ability to engage in intensive physical activity. In advanced cases, patients may become bedridden.

Existing treatments include drugs and LVAD units, which take over some of the hearts function to relieve stress. Some drugs may help the heart work more efficiently, but none have been shown to improve heart failure by actually regenerating lost heart muscle.

Stem cell therapy is tested in patients who havent responded well to other treatments. Trials have been and are being conducted in San Diego area hospitals.

Scripps Health has been testing a cardiac stem cell therapy from Los Angeles-based Capricor. The cells, taken from donor hearts, are injected into the coronary artery, where they are expected to settle in the heart and encourage regrowth.

UC San Diego is testing a heart failure therapy from Teva Pharmaceutical Industries. It consists of bone marrow derived mesenchymal precursor cells. These can give rise to several different cell types, including muscle cells.

And many other trials are going on throughout the country and internationally.

Adler and Schatz said theres reason for optimism in the long run, as technologies improve.

Just because the other trials have been negative doesnt mean this technique wont be beneficial, Adler said. Its just too early to tell.

That said, Schatz emphasized that the nature of the three-phase clinical trial process means that the show-stoppers for a treatment typically appear late.

Tighter standards needed

Clean trials trials where we all agree that this is the patient population we want to look at, are needed, he said.

For example, heart failure comes in two types, he said. Ischemic heart failure is caused by heart attacks and blocked arteries, which impede blood flow. Non-ischemic heart failure can be caused by damage from diseases, such as a virus.

Non-ischemics can be younger people, in their 20s and 30s, while the ischemic patients are older. Mixing those patient groups in a single trial is a mistake, he said.

Theyre different animals, Schatz said.

Another pitfall is failing to screen carefully enough to enroll only patients likely to benefit, Schatz said.

You can have a patient who has chest pain, and coronary disease just incidentally, he said.

His shoulder or chest pain is from a virus. So he goes into the trial and gets a placebo injection in his arm of cortisone, and his arm pain goes away. And because hes in that placebo group, hes counted as a success the pain went away. It has nothing to do with his heart. Thats an extreme example, but we actually saw that happen.

In a failed gene therapy trial for heart disease, some patients apparently had received the injection in the wrong location, missing the heart muscle, Schatz said.

You assume they got the gene, but they didnt, Schatz said. The study was negative, and thats why I think it was negative.

Such errors dont show up in Phase 1 trials, Adler and Schatz said, because theyre focused on evaluating safety. And these early trials dont have many patients, there arent enough to comfortably determine the therapy is really effective.

By the last stage of the trial, these sources of error have often been identified and trial standards have tightened up. And thats when the faulty assumptions made early appear as the trial ends in failure.

Despite those forbidding hurdles, Adler said research should continue.

This disease is killing a lot of people. Theres not going to be enough hearts to go around for transplant. Theres six million Americans with heart failure, and theres 2,000 heart transplants a year. So coming up with novel regenerative cell-based therapy is something were still excited about.

bradley.fikes@sduniontribune.com

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Study: heart failure stem cell therapy safe, shows early signs of effectiveness - The San Diego Union-Tribune

Eddie Marks is the pioneer in the University of Delaware Department of Medical Laboratory Sciences. Hes the first Ph.D. graduate in program history.

Having completed a professional masters degree in business/biotechnology at UD, Marks jumped at the opportunity of a fledging Ph.D. in the medical sciences program. Of course, Marks was interested in the programs core courses like statistics, immunology and physiology, but the department also granted the aspiring researcher a great deal of independence.

There is a lot of freedom to be able to choose, which is what I really liked coming in, explained Marks, who researches how adult bone narrow stem cells can treat heart attacks. I took a biology ethics course and a materials science course, which, by learning some of the engineering, really helped to further my research.

With a microbiology background, Marks was used to growing cells and working under a microscope, which eased his translation into the field. He was motivated by his adviser Arun Kumar, who also took an interdisciplinary route. Kumar took an organic chemistry background and applied it to nanomedicine. As a masters students, Marks was tapped to work on a stem cell project with Kumar. He took the preliminary data and worked on turning the stem cells into tissue types.

But research is far from Marks only talent. Elsevier Health reached out to Kumar about a book on thymosins, a protein class with diverse biological activities. Kumar and Marks had used one of these thymosin proteins specific to the heart thymosin beta-4 to turn stem cells into heart tissue. So the pair drafted a book chapter on how this protein helps heal our most vital internal organ.

We looked at [the proteins] role in development as the heart is growing, its natural effects after a heart attack, how the protein gets released and how we and other researchers use it to attempt to heal the heart after certain cardiac events, said Marks.

Earlier this month, Marks successfully defended his dissertation Adult Human Bone Marrow Mesenchymal Stem Celled Primed for the Repair of Damaged Cardiac Tissue after Myocardial Infarction. Half of the numbered chapters of the dissertation were published or are currently under review in scientific journals. Each of the six chapters of the dissertation is a paper to be published.

With his Ph.D. in hand, Marks is headed to private industry, which could mean consulting or science writing.

I want to be client-facing and help an array of companies.

Combining the time spent on the masters and Ph.D. program, Marks completed the two degrees in only five and a half years. Around the country, the typical student finishes similar programs between six and eight years time. He credits the department for the unique program design and streamlined process.

The department is very connected to the hospital [Christiana Care] and has a good reputation at the University, said Marks. The faculty knows every group from biology to engineering to the Life Science Research Facility and down to STAR Campus. There are connections everywhere. My dissertation committee had incredibly varied areas of expertise and that would not happen without Medical Laboratory Sciences.

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First Ph.D. recipient - UDaily

Early efforts to harness the potential of stem cells for treating disease were largely focused on regeneration and the ability to repair tissues in the body through cell therapies. However, as technologies have advanced, the focus is shifting to using stem cells in drug discovery applications, such as compound screening, toxicity testing, target identification, and disease modelling. Professor Christine Mummery, from the University of Leiden tells us more and explains why stem cells are particularly suited to these applications.

Why use stem cells?

What is it that makes stem cells such an attractive option for drug discovery studies? One of the main reasons is that they make a much better model of human disease and drug reactions than animal models. As Professor Christine Mummery explains, many commonly used animal models such as mice do not accurately reflect some of the workings of cells and processes in the human body, having different immune systems and characteristics, such as heart rate, for example. This can result in problems with drugs falling down in clinical trials after showing promising results in earlier animal studies.

Using more relevant models provides not only financial savings by highlighting issues earlier in the drug discovery pipeline, but also helps efforts to reduce the number of animals used in research.

Stem cells in toxicity testing

A vital part of determining a drugs safety is assessing its cardiac toxicity. This refers to the side effects a drug can have on the functioning of the heart, such as causing arrhythmias and sudden death. As well as ensuring the safety of a drug, however, there is also a need to not unduly constrain drug development. Improvements in assay design and the implementation of the Comprehensive in Vitro Proarrhythmia Assays (CiPA) are helping to find a balance in this area.

Professor Christine Mummery tells us more about the problem of cardiotoxicity and how stem cell models and CiPA can help.

Stem cells can also play a role in testing the systemic toxicity of drugs. As Dr Glyn Stacey from NIBSC explains, pluripotent stem cell lines are increasingly being used to develop new assays that enable earlier identification of drugs that can have chronic effects on the body.

Endogenous activation of stem cells A novel and promising area of currently developing research is the ability to drive regeneration endogenously using small molecules. As Professor Angela Russell from the University of Oxford describes in the following video, we might not need to rely on using stem cells themselves, but rather small molecule therapeutics that can promote repair in damaged tissues. Circumventing the need for cells could have huge benefits for both the patient and drug developers.

What are some of the hurdles?

Stem cells certainly provide numerous opportunities to accelerate the drug discovery field, but challenges do remain.

A fundamental issue faced by all researchers in this field is ensuring the quality of the cells used. As Dr Glyn Stacey explains, a good level of quality control needs to be maintained throughout, to ensure that cells have not been contaminated or mixed up with another cell line.

Understanding signalling pathways and knowing which growth factors to add to push cells to develop into progenitor cells can also present challenges to researchers developing stem cell based screening assays. Producing sufficient numbers of relevant cell types to conduct a screen is another problem commonly faced.

The final hurdle is translation to the clinic, which relies on proving the safety of a treatment, and ensuring that it does not give rise to secondary conditions. In the case of Professor Angela Russells work, this involves taking careful steps to select compounds that act through correct pathways that wont increase the risk of cancer developing.

What does the future hold?

The roles that stem cells play in the drug discovery process are likely to continue to increase, as developments in technology enable the creation of a wider range of cells and assays. A move towards using cells with greater maturity and models that incorporate a combination of different cell types, enabling the study of interactions between cells is on the horizon. These combinations of cells will teach us a lot about drug discovery and disease, says Professor Christine Mummery.

All interviews from Stem Cells in Drug Discovery 2017 can be found here.

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Stem Cells in Drug Discovery | Technology Networks - Technology Networks

Junnan Tang Deliang Shen Thomas George Caranasos Zegen Wang Adam C Vandergriff Tyler A Allen Michael Taylor Hensley Phuong-Uyen Dinh Jhon Cores Tao-Sheng Li Jinying Zhang Quancheng Kan Ke Cheng PubMedID: 28045024

Tang J, Shen D, Caranasos TG, Wang Z, Vandergriff AC, Allen TA, Hensley MT, Dinh PU, Cores J, Li TS, Zhang J, Kan Q, Cheng K. Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome. Nat Commun. 2017;813724.

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell-cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as 'synthetic stem cells' which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.

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Stem cells under a microscope.

A newly published study shows for the first time that if cardiac stem cells are eliminated, the heart is unable to repair itself after damage.

Researchers at Kings College London have for the first time highlighted the natural regenerative capacity of a group of stem cells that reside in the heart. This new study shows that these cells are responsible for repairing and regenerating muscle tissue damaged by a heart attack which leads to heart failure.

The study, published in the journal Cell, shows that if the stem cells are eliminated, the heart is unable to repair after damage. If the cardiac stem cells are replaced the heart repairs itself, leading to complete cellular, anatomical and functional heart recovery, with the heart returning to normal and pumping at a regular rate.

Also, if the cardiac stem cells are removed and re-injected, they naturally home to and repair the damaged heart, a discovery that could lead to less-invasive treatments and even early prevention of heart failure in the future.

The study, funded by the European Commission Seventh Framework Program (FP7), set out to establish the role of cardiac stem cells (eCSCs) by first removing the cells from the hearts of rodents with heart failure. This stopped regeneration and recovery of the heart, demonstrating the intrinsic regenerative capacity of these cells for repairing the heart in response to heart failure.

Heart failure when the heart is unable to pump blood around the body adequately affects more than 750,000 people in the UK, causing breathlessness and impeding daily activities. Current treatments are aimed at treating the underlying causes, such as coronary heart disease, heart attack and blood pressure through lifestyle changes, medicines and in severe cases, surgery. These treatments are sometimes successful in preventing or delaying heart failure. However, once heart failure develops the only curative treatment is heart transplantation.

By revealing this robust homing mechanism, which causes cardiac stem cells to home to and repair the hearts damaged muscle, the findings could lead to less invasive treatments or even preventative measures aimed at maintaining or increasing the activity of the hearts own cardiac stem cells.

Dr Georgina Ellison, the first author of the paper and Professor Bernardo Nadal-Ginard, the studys corresponding author, both from the Center of Human & Aerospace Physiological Sciences and the Center for Stem Cells and Regenerative Medicine at Kings, said: In a healthy heart the quantity of cardiac stem cells is sufficient to repair muscle tissue in the heart. However, in damaged hearts many of these cells cannot multiply or produce new muscle tissue. In these cases it could be possible to replace the damaged cardiac stem cells or add new ones by growing them in the laboratory and administering them intravenously.

Dr Ellison added: Understanding the role and potential of cardiac stems cells could pave the way for a variety of new ways to prevent and treat heart failure. These new approaches involve maintaining or increasing the activity of cardiac stem cells so that muscle tissue in the heart can be renewed with new heart cells, replacing old cells or those damaged by wear and tear.

The cardiac stem cells naturally home to the heart because the heart is their home they know to go there. Current practices involve major operations such as injection through the hearts muscle wall (intramyocardial) or coronary vessels (intracoronary). The homing mechanism shown by our research could lead to a less invasive treatment whereby cardiac stem cells are injected through a vein in the skin (intravenously).

Professor Nadal-Ginard added: Although an early study, our findings are very promising. Next steps include clinical trials, due to start early 2014, aimed at assessing the effectiveness of cardiac stem cells for preventing and treating heart failure in humans.

Publication: Georgina M. Ellison, et al., Adult c-kitpos Cardiac Stem Cells Are Necessary and Sufficient for Functional Cardiac Regeneration and Repair, Cell, Volume 154, Issue 4, 827-842, 2013; doi:10.1016/j.cell.2013.07.039

Source: Kings College London

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Cardiac Stem Cells Offer New Ways to Prevent and Treat ...

SOUTH SAN FRANCISCO, CA--(Marketwired - March 29, 2017) - VistaGen Therapeutics Inc. (VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, announced today that the European Patent Office (EPO) has issued a Notice of Intention to Grant the Company's European Patent Application for AV-101, its oral CNS prodrug candidate in Phase 2 development for major depressive disorder (MDD). The granted claims covering multiple dosage forms of AV-101, treatment of depression and reduction of dyskinesias associated with L-DOPA treatment of Parkinson's disease will be in effect until at least January 2034.

"We are extremely pleased to receive the EPO's notice of intention to grant significant CNS-related patent claims for AV-101, another substantial step forward in our plan to secure a broad spectrum of intellectual property protection for AV-101 covering multiple CNS indications," stated Shawn Singh, Chief Executive Officer of VistaGen.

About AV-101

AV-101 (4-CI-KYN) is an oral CNS prodrug candidate in Phase 2 development in the U.S. as a new generation treatment for major depressive disorder (MDD). AV-101 also has broad potential utility in several other CNS disorders, including chronic neuropathic pain and epilepsy, as well as neurodegenerative diseases, such as Parkinson's disease and Huntington's disease.

AV-101 is currently being evaluated in a Phase 2 monotherapy study in MDD, a study being fully funded by the U.S. National Institute of Mental Health (NIMH) and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH, as Principal Investigator.

VistaGen is preparing to advance AV-101 into a 180-patient, U.S. multi-center, Phase 2 adjunctive treatment study in MDD patients with an inadequate response to standard FDA-approved antidepressants, with Dr. Maurizio Fava of Harvard University as Principal Investigator.

About VistaGen

VistaGen Therapeutics, Inc. (VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is a new generation oral antidepressant drug candidate in Phase 2 development for major depressive disorder (MDD). AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressants. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Company's Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, Parkinson's disease and Huntington's disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit.

VistaStem Therapeutics is VistaGen's wholly owned subsidiary focused on applying human pluripotent stem cell technology, internally and with collaborators, to discover, rescue, develop and commercialize proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases, and cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. In December 2016, VistaGen exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.

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For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2 (monotherapy) and/or the Company's planned Phase 2 (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Therapeutics Receives European Patent Office Notice of Intention to Grant European Patent for AV-101 - Yahoo Finance

Heart tissue grown on spinach leaves: Researchers turn to the ... Science Daily Researchers face a fundamental challenge as they seek to scale up human tissue regeneration from small lab samples to full-size tissues and organs: how to ... and more »

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Heart tissue grown on spinach leaves: Researchers turn to the ... - Science Daily

SmartNews Keeping you current

smithsonian.com March 27, 2017 1:36PM

Researchers have gotten pretty good at growing human tissues from stem cellsfrom heart cellsin a Petri dish to 3-D printingfull ears. But assembling the complex vascularity of heart tissue is no small feat. Even the most sophisticated 3-D printers can't fabricate the structure. However, asBen Guarinowrites for The Washington Post, researchers at Worcester Polytechnic Institute might have a solution: use spinach leaves as the backbone for the heart tissue.

The study, recently published in the journalBiomaterials, offers an innovative wayto solve a common problem in tissue engineering by looking towardthe plant world. Though plants and animals transport fluids in very different ways,their vascular structuresare similar, according to apress release.

Take a plant leaf and hold it up to the light. "What do you see?"Tanja Dominko, an author of the study, asksCyrusMoultonat theWorcester Telegram. "You see a plant vascular system that is very, very similar to a human system and serves an identical purpose, she says.

But to use that structure, researchers had to first remove the plant cells, leaving its vascular system intact. To accomplish such a feat, the team washes the leaves through using a type of detergent, turning the leaf from transparent green to translucent white. The remaining cellulose structure is compatible with human tissue.

As Guarino reports,the researchers then seeded the spinach with cardiac tissue, which began to grow inside the leaf. After five days, they witnessed some of the tissue contracting on the microscopic level. In other words, the spinach leaf began to beat. They passed liquids and microbeads the size of human blood cells through the leaves to show they could potentially transport blood.

Though the team wasn't aiming to grow a fullheart from spinach,they hope the methodcould be used to help patients after suffering from heart attack or other heart problem. Long term, were definitely envisioning implanting a graft in damaged heart tissue, Glenn Gaudette, a bioengineer and co-author of the study, tells Guarino. They hope to make a patch as thick and strong as natural heart tissue.

Spinach is not the only superfood the team is working with. According to the press release, they have also successfully removed the cells from leaves of parsley, sweet wormwood and hairy peanut root. In the future, different plants could be used as scaffolding to grow different patches and replacement parts. For instance, the hollow stem of jewelweed could be sued to create arteries and wood or bamboo could be used to engineer bone. When you think of the wide array of plants out there, theres almost nothing that plants can't do, Gaudette tells Moulton.

The Worcester team isnt the only group working on this idea either. Andrew Pelling at the University of Ottawa is using the cellulose in apple slicesto grow (slightly scary-looking) human ears.

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Jason Daley is a Madison, Wisconsin-based writer specializing in natural history, science, travel, and the environment. His work has appeared in Discover, Popular Science, Outside, Mens Journal, and other magazines.

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Researchers Turn Spinach Leaves Into Beating Heart Tissues - Smithsonian

By FPJ Bureau|Mar 20, 2017 06:26 pm

Melbourne: Scientists have created a functional beating human heart muscle from stem cells, a significant step forward in cardiac disease research. Researchers at The University of Queensland (UQ) in Australia developed models of human heart tissue in the laboratory so they can study cardiac biology and diseases in a dish.

The patented technology enables us to now perform experiments on human heart tissue in the lab, said James Hudson from the UQ School of Biomedical Sciences. This provides scientists with viable, functioning human heart muscle to work on, to model disease, screen new drugs and investigate heart repair, said Hudson.

In the laboratory we used dry ice to kill part of the tissue while leaving the surrounding muscle healthy and viable, Hudson said. We found those tissues fully recovered because they were immature and the cells could regenerate in contrast to what happens normally in the adult heart where you get a dead patch. Our goal is to use this model to potentially find new therapeutic targets to enhance or induce cardiac regeneration in people with heart failure, he said.

Studying regeneration of these damaged, immature cells will enable us to figure out the biochemical events behind this process. Hopefully we can determine how to replicate this process in adult hearts for cardiovascular patients, said Hudson.

Each year, about 54,000 Australians suffer a heart attack, with an average of about 23 deaths every day, researchers said. Heart Foundation Queensland CEO Stephen Vines said the charity was excited to fund such an important research project.

Heart attack survivors who have had permanent damage to their heart tissue are essentially trying to live on half an engine, Vines said. The research will help unlock the key to regenerating damaged heart tissue, which will have a huge impact on the quality of life for heart attack survivors, he added.

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Human heart muscle made from stem cells - Free Press Journal

A stem cell-derived heart muscle cell. Proteins that are important for muscle cell contraction are highlighted in red and green, and cell nuclei are blue. Credit: Joseph C. Wu, M.D., Ph.D., Stanford Cardiovascular Institute

Using human heart cells generated from adult stem cells, researchers have developed an index that may be used to determine how toxic a group of cancer drugs, called tyrosine kinase inhibitors (TKIs), are to human cells. While 26 TKIs are currently used to treat a variety of cancers, some can severely damage patients hearts, causing problems such as an irregular heartbeat or heart failure.

For the study, reported February 15 in Science Translational Medicine, the researchers used stem cell-derived heart cells from 13 volunteers to develop a cardiac safety index that measures the extent to which TKIs kill or alter the function of heart cells. They found that the TKIs' toxicity score on the index was generally consistent with what is known about each drug's heart-related side effects.

This work follows on the heels of an earlier study from the same research team, published in Nature Medicine, in which they assessed the heart cell toxicity of doxorubicin, a chemotherapy drug that also causes heart-related side effects, including heart failure. In that study, the researchers used stem cell-derived heart cells from women with breast cancer to correctly predict how sensitive each womans heart cells were to doxorubicin.

Such tests could ultimately help the pharmaceutical industry identify drugs that cause heart-related side effects earlier in the drug development process and help the Food and Drug Administration (FDA) during the drug review and approval process, said the study's senior author Joseph C. Wu, M.D., Ph.D., director of the Stanford Cardiovascular Institute.

I hope this research will be helpful for individual patients, once we further implement precision medicine approaches, he added.

Ranking Heart Toxicity

To assess the potential risk of heart toxicity for drugs in development, pharmaceutical companies use laboratory tests involving animals (usually rats or mice) or cells from animals or humans that are engineered to artificially express heart-related genes. Drug candidates that appear to have an acceptable balance of benefits and risks typically proceed to testing in human clinical trials.

But there can be biological differences between these existing models and humans, so non-clinical lab tests can have significant limitations, explained Dr. Wu.

Currently, the first time humans are exposed to a new drug is during clinical trials, he said. We think it would be great if you could actually expose patients heart, brain, liver, or kidney cells to a drug in the lab, prior to clinical treatment, allowing researchers to determine whether the drug has any toxic effects.

Dr. Wu, a cardiologist by training, studies toxicities cancer drugs cause in heart cells. Human heart muscle cells (called cardiomyocytes), however, are hard to obtainrequiring risky heart surgery that may be of no direct benefit to the patientand are notoriously difficult to grow in the lab.

As an alternative, researchers have developed a method to produce heart cells from human induced pluripotent stem cells (hiPSCs). hiPSCs are created by genetically engineering normal human skin or blood cells to express four specific genes that induce them to act like stem cells. Chemical treatments can prompt hiPSCs to develop into mature cell types, such as heart muscle cells.

A large body of research has established that human adult stem cell-derived heart cells, which function and grow in cell culture, can be used as an initial model to screen drug compounds for toxic effects on the heart, said Myrtle Davis, Ph.D., chief of the Toxicology and Pharmacology Branch of NCIs Division of Cancer Treatment and Diagnosis, who was not involved in the studies.

For the Science Translational Medicine study, Dr. Wu and his colleagues set out to determine if a panel of human stem cell-derived heart cells could be used to evaluate the heart toxicity of 21 different FDA-approved TKIs.

They generated hiPSC-derived heart endothelial, fibroblast, and muscle cells from 13 volunteers: 11 healthy individuals and 2 people with kidney cancer who were being treated with a TKI. Using drug concentrations equivalent to what patients receive, the investigators next determined how lethal each TKI was to the heart cells.

They found that several TKIs were very lethal to endothelial, fibroblast, and heart muscle cells from all 13 individuals, while others were more benign.

Stem cell-derived heart muscle cells grown in a dish spontaneously contract as a beating heart does, so the researchers also analyzed the effects of TKIs on the cells beat rate, or contractility. They found that several TKIs altered the cells beat rate before they were killed by the drug treatment. If severe enough, an irregular heartbeat (called an arrhythmia), can disrupt normal heart function.

From these lethality and contractility experiments, the team developed a cardiac safety index, a 0-to-1 scale that identifies how toxic a TKI is to heart cells (with 0 being the most toxic). They then used the index to rank the 21 TKIs. The control treatment scored a 1, while a few TKIs that are labeled by the FDA with boxed warnings for severe heart toxicity scored close to 0.

Safety indices like this one can be very useful during drug discovery, said Dr. Davis, and the applicability of the index developed by Dr. Wu and his colleagues will become clear when they evaluate its performance with more compounds.

And for the safety index to be applicable to more patients, the panel of cells used to develop it would need to be gathered from a sufficiently representative population of people reflecting different ages, races/ethnicities, health statuses, and other characteristics, said Lori Minasian, M.D., deputy director of NCIs Division of Cancer Prevention, who was not involved in either study.

For example, the study did not include cells derived from patients with [pre-existing] cardiac disease, said Dr. Davis.

A Personalized Approach

In addition to their potential application during drug development, Dr. Wu believes that stem cell-derived heart cells could potentially be used to predict toxicity risk for individual patients. He and his colleagues explored this possibility in their Nature Medicine study.

Doxorubicin, used on its own or in combination with other drugs, is an effective treatment for breast cancer and several other types of cancer. Like TKIs, however, it is known to cause heart toxicities, such as arrhythmias and heart failure, in a small proportion of patients. But there has been no way to predict which patients will experience these side effects.

The researchers developed stem cell-derived heart cells from eight women with breast cancer who had been treated with doxorubicinhalf of whom experienced cardiotoxicity from the treatment and half who did not.

In several different lab tests, the heart cells from women who had experienced cardiotoxicity were more sensitive to doxorubicin than those from women who had not. More specifically, in heart cells from women who had experienced cardiotoxicity, doxorubicin treatment caused more severe irregularities in cell contractility, and even low concentrations of the drug killed the cells.

An Improved Model

While the stem cell-derived heart cell model may be an improvement over the current [drug testing] system, its not perfect, said Dr. Minasian. For example, the model does not capture contributions of other organs and cells to the toxic effects of a drug, she explained. The drug may be broken down in the liver, for instance, and side products (called metabolites) may also cause toxic effects.

In addition, the lab-grown stem cell-derived version of someones heart cells are not going to be exactly the same as the cells found in that persons heart, Dr. Wu noted. Nevertheless, they reflect the same genetics and they are pretty good at predicting drug response, he said.

Looking forward, Dr. Minasian said, figuring out how to best use this approach is going to take more work, but being able to better predict human response [to cancer drugs] is important.

The research teams next steps include conducting prospective studies to determine whether they can use a patients stem cell-derived heart cells to potentially predict if that person will develop heart toxicity before they actually receive cancer treatment.

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

Reference

Sharma, A., Burridge, P. W., McKeithan, W. L., Serrano, R., Shukla, P., Sayed, N., ... & Matsa, E. (2017). High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Science translational medicine, 9(377), eaaf2584.

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Measuring Heart Toxicity of Cancer Drugs | Technology Networks - Technology Networks

Published: March 22 2017

Stanford University School of Medicine researchers grew heart muscle cells and used them, along with CRISPR, to predict whether a patient would benefit or experience bad side effects to specific therapeutic drugs

What would it mean to pathology groups if they could grow heart cells that mimicked a cardiac patients own cells? What if clinical laboratories could determine in vitro, using grown cells, if specific patients would have positive or negative reactions to specific heart drugs before they were prescribed the drug? How would that impact the pathology and medical laboratory industries?

We may soon know. Researchers at Stanford University School of Medicine (Stanford) have begun to answer these questions.

May Be Feasible for Clinical Laboratories to Use Pluripotent Stem Cells for Assays

In a Stanford press release, researchers stated that induced pluripotent stem cells (iPS cells), coupled with CRISPRtechnology, could be used to determine:

1) Whether a patient would benefit from a specific therapeutic drug; and

2) The likelihood that the patient might have a negative reaction or bad side effect from that drug.

Thirty percent of drugs in clinical trials are eventually withdrawn due to safety concerns, which often involve adverse cardiac effects. This study shows that these cells serve as a functional readout to predict how a patients heart might respond to particular drug treatments and identify those who should avoid certain treatments, said Joseph Wu, MD, PhD, in the Stanford press release. Wu is Director of Stanfords Cardiovascular Institute and a Professor of Cardiovascular Medicine and Radiology.

The researchers believe their discovery could become a form of diagnostic and prognostic testing performed by pathologists and clinical laboratories if it passes further clinical trials.

Heart Muscle Made from Stem Cells, Study Advances Precision Medicine

The iPS cells are stem cells created in a lab, usually from a persons skin sample, and then induced into becoming cells from other parts of the body. Heart muscle cells made from iPS cells mirror the expression patterns of key genes in the donors native heart tissue. This means the cells can be leveraged to predict a patients likelihood of experiencing drug-related heart damage, according to the Stanford release.

The Stanford study also advanced precision medicine. It combined genetics, large-scale data research, and individualized testing to determine the best treatments for patients, noted an article in United Press International (UPI).

Researchers were motivated by a need to understand individual susceptibility to drug-induced cardiotoxicity, to improve patient safety, and to prevent drug attrition, according to the Stanford study, which was published in the research journal Cell Stem Cell.

Human iPS cells enable the study of pharmacological and toxicological responses in patient-specific cardiomyocytes and may serve as preclinical platforms for precision medicine, the authors noted in the study summary.

Furthermore, the researchers idea could have implications for medical conditions beyond cardiomyopathy, noted an article in LabRoots.

Cardiomyopathy is a disease of the heart muscle that affects millions of people worldwide each year.

Joseph Wu, MD, PhD (above left), and Elena Matsa, PhD (above right), both with Stanford University School of Medicine, led a team of researchers who published a study involving CRISPR that suggests heart muscle cells made from induced pluripotent stem cells (iPS cells) could be used to identify cardiac patients who could benefit from or who could be damaged by certain cardiac medications. (Photo credits: Stanford University.)

Testing Tissues in the Stanford University Research Lab

Heres how the research progressed, according to the Stanford press release:

Matsa, Wu, and their colleagues created heart muscle cells, or cardiomyocytes, from iPS cells taken from seven people not known to be genetically predisposed to cardiac problems;

They sequenced the RNA molecules made by the heart muscle cells to learn which proteins the cells were making, and by how much;

They then compared the results within individualslooking at the gene expression patterns of cardiomyocytes derived from several batches of iPS cells from each personas well as among all seven study subjects.

They also investigated how the cardiomyocytes from each person responded to increasing amounts of two drugs: Rosiglitazone (marketed as Avandia by GlaxoSmithKline), which is sometimes used to treat Type 2 diabetes; and Tacrolimus (marketed as Prograf by Astellas Pharma), which serves as an immunosuppressant to inhibit the rejection of transplanted organs. Each of the two drugs has been associated with adverse cardiac effects in some people, but it has not been possible to predict which patients will experience heart damage.

Gene expression patterns of the iPS cell-derived cardiomyocytes from each individual patient correlated very well, said Elena Matsa, PhD, Stanford Instructor, Cardiovascular Institute, and the studys lead author. But there was marked variability among the seven people, particularly in genes involved in metabolism and stress responses. In fact, one of our subjects exhibited a very abnormal expression of genes in a key metabolic pathway.

Gene Editing Reveals Drug Response Information

Enter the Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR (pronounced crisper), gene editing technology. CRISPR technology has advanced the study and practice of genetic medicine.

Researchers could not pinpoint a specific gene mutation responsible for abnormal cardiomyocyte response. But they did identify a metabolic pathway that influenced Rosiglitazones response.

They corrected the abnormality using CRISPR-Cas9 (a simplified version of the CRISPR/Cas system). This genome editing technique enables researchers to edit parts of the genome by removing or changing in some manner the DNAsequence, according to yourgenome, an information website dedicated solely to DNA, genes, and genomes.

The results? The Stanford researchers reported boosting a gene expression in the pathway, restoring normal function, and prompting a response to Rosiglitazone that was consistent to that of the other subjects cardiomyocytes.

Clinical Laboratories Become Even More Integral to Cardiac Diagnosis and Treatment

Can iPS-derived cardiomyocytes reliably replicate human heart tissue? Researchers were not sure. So, they created iPS cells from another three people who had heart biopsies or transplants. They then compared the cells made in the clinical laboratory with the gene native cells and found that they were similar in many significant ways.

In the end, cardiomyocytes derived from human iPS cells correlated with patient participants in the Stanford study. And, most importantly, the study revealed a potential ability to test drugs for adverse reactions and improve treatment for millions of people with cardiomyopathy. Should additional research confirm these findings, it could provide medical laboratories with a new approach to improving diagnosis and therapeutic selection for patients with heart disease.

Donna Marie Pocius

Related Information:

Heart Muscle Grown from Stem Cells May Help Doctors Test Treatments

Heart Muscle Made from Stem Cells Aids Precision Cardiovascular Medicine

Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses in Vitro

Heart Stem Cells for Individualized Medicine in Cardiology

Stem Cells Create Faithful Replicas of Native Tissues, According to Stanford Study

CRISPR/Cas9 and Targeted Genome Editing: A New Era in Molecular Biology

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Pathologists and Clinical Laboratories May Soon Have a Test for Identifying Cardiac Patients at Risk from Specific ... - DARKDaily.com - Laboratory...

Scientists at The University of Queensland have taken a significant step forward in cardiac disease research by creating a functional beating human heart muscle from stem cells.

Dr James Hudson and Dr Enzo Porrello from the UQ School of Biomedical Sciences collaborated with German researchers to create models of human heart tissue in the laboratory so they can study cardiac biology and diseases in a dish.

The patented technology enables us to now perform experiments on human heart tissue in the lab, Dr Hudson said.

This provides scientists with viable, functioning human heart muscle to work on, to model disease, screen new drugs and investigate heart repair.

The UQ Cardiac Regeneration Laboratory co-leaders have also extended this research and shown that the immature tissues have the capacity to regenerate following injury.

In the laboratory we used dry ice to kill part of the tissue while leaving the surrounding muscle healthy and viable, Dr Hudson said.

We found those tissues fully recovered because they were immature and the cells could regenerate in contrast to what happens normally in the adult heart where you get a dead patch.

Our goal is to use this model to potentially find new therapeutic targets to enhance or induce cardiac regeneration in people with heart failure.

Studying regeneration of these damaged, immature cells will enable us to figure out the biochemical events behind this process.

Hopefully we can determine how to replicate this process in adult hearts for cardiovascular patients.

Each year, about 54,000 Australians suffer a heart attack, with an average of about 23 deaths every day.

The UQ research has been supported by the National Health and Medical Research Council (NHMRC) and the National Heart Foundation.

Heart Foundation Queensland CEO Stephen Vines said the charity was excited to fund such an important research project.

Heart attack survivors who have had permanent damage to their heart tissue are essentially trying to live on half an engine, Mr Vines said.

The research by Dr Hudson and Dr Porello will help unlock the key to regenerating damaged heart tissue, which will have a huge impact on the quality of life for heart attack survivors.

Dr Hudson and Dr Porello are deserved recipients of our highest national research accolade the Future Leader Fellowship Award.

Reference:

Tiburcy, M., Hudson, J. E., Balfanz, P., Schlick, S. F., Meyer, T., Liao, M. C., . . . Zimmermann, W. (2017). Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair. Circulation. doi:10.1161/circulationaha.116.024145

This article has been republished frommaterialsprovided by University of Queensland. Note: material may have been edited for length and content. For further information, please contact the cited source.

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'Beating' Heart Created from Stem Cells - Technology Networks

A team of scientists has developed a new safety index for a common group of chemotherapy drugs, by using a stem cell model to screen such therapies for their potential to damage patients hearts.

The study, published in Science Translational Medicine, was co-authored by Paul Burridge, PhD, assistant professor of Pharmacology.

Tyrosine kinase inhibitors (TKIs), a class of chemotherapy drugs, have become increasingly important in treating many types of cancer. But almost all TKIs are also associated with cardiovascular side effects ranging from arrhythmias to heart failure and there has not yet been an effective tool to predict this cardiotoxicity.

In the current study, the scientists demonstrated that human-induced pluripotent stem cells can be used to model how TKIs might affect the hearts of patients receiving chemotherapy.

To do so, the scientists took stem cells from both a control group and patients with cancer and reprogrammed them to become cardiomyocytes, or heart muscle cells. Using high-throughput screening, they then evaluated how the heart cells responded to treatment with 21 different FDA-approved TKIs, looking at factors like cell survival, signaling and alterations in their ability to beat properly.

With the stem-cell data, the scientists were able to create a cardiac safety index, which ranks the TKIs on their likelihood of inflicting heart damage. That index correlates with the toxicity that has been observed in patients clinically a validation that suggests the screening system might be a powerful tool in predicting toxicity before therapies are ever administered to patients.

Future research could establish even more specific predictions, by comparing the genomes of patients who might experience a certain drug side effect, such as atherosclerosis, with those who dont. Long-term, what my lab is interested in is taking a patients whole genome and, based on the work weve done in the past, being able to predict whether a patient will have an adverse drug event, said Burridge, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. This is the whole idea of pharmacogenomics, or precision medicine: Everyone is going to have a different response to a drug, and that response good or bad is already encoded in all of us.

In the study, the scientists also discovered that administering insulin or insulin-like growth factor 1 alongside TKIs seemed to protect against some of the heart damage associated with the drugs. While its still early, this is the first step toward opening up a whole new field of identifying cardioprotectants to reduce the toxicity of these drugs, Burridge said.

This article has been republished frommaterialsprovided byNorthwestern University, Feinberg School of Medicine. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Stem Cell Cardiac Toxicity Model for Testing Chemotherapy Agents - Technology Networks