Page 21234..1020..»

Archive for the ‘Cardiac Stem Cells’ Category

Can Tiny Plumbing Fix Broken Hearts? – NC State News

Illustration of the heart patch using artificial capillaries.

Editors note: This is a guest post by Frances Ligler, Lampe Distinguished Professor in the Joint Department of Biomedical Engineering (BME) at NC State and UNC-Chapel Hill. This is one of a series of posts from NC State researchers that address the value of science, technology, engineering and mathematics.

Judging from evidence provided by Star Wars and The Six Million Dollar Man, repairing body parts seems to require a screwdriver. However, teams of scientists and engineers are exploring other ways to repair our bodies and NC State faculty and students are collaborating across colleges to perform cutting-edge experiments to further regenerative medicine therapeutics.

Before joining NC State, Michael Daniele (an assistant professor of BME and electrical and computer engineering) and I invented a method of making long strings of artificial blood capillaries by creating soft walls in between fluids streaming through a small channel. Cells present in the streams were incorporated into the capillaries to mimic the 3-D architecture of your capillaries and veins.

At NC State, we joined forces with Ke Cheng, an expert in stem cells and cardiology from the College of Veterinary Medicine, to incorporate these artificial capillaries into a degradable patch containing cardiac stem cells. Postdoctoral fellow Teng Su placed the patches on damaged areas of rat hearts and showed both repair of the rat heart tissue and return of the pumping capacity of the heart (which does not happen under the untreated condition where scar tissue forms in the damaged heart).

In another exciting collaboration, Matt Fisher from BME, Rohan Shirwaiker (an associate professor of industrial and systems engineering) and Behnam Pourdeyhimi from the College of Textiles are teaming up to reconstruct damaged knees. They are recreating the underlying fibrous scaffolds that support the cartilage in a manner that better mimics the original knee and supports the growth of the normal cell type within the new scaffolds which should improve healing and support a return to normal function in the knee.

The variety of skills required for this project include designing an entirely new device for printing fibers, understanding how to arrange the fibers and change their composition to accommodate bone or cartilage-forming cells, and learning how the new tissue develops to accommodate physical motion.

The lure of replacement body parts is widespread. There are far more people waiting for replacement organs than can be accommodated by human donors. Learning to use an individuals own cells to trigger tissue regeneration has far more long-term potential to address the ever-growing needs of accident victims and an aging population.

The key to success lies with teams of dedicated scientists, engineers, medical professionals and financial supporters that are focused on using the lessons learned across many fields to solve this grand challenge.

Original post:
Can Tiny Plumbing Fix Broken Hearts? – NC State News

SpaceX to launch heart, bone health experiments to space station Thursday – CU Boulder Today

A SpaceX rocket is slated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

Original post:
SpaceX to launch heart, bone health experiments to space station Thursday – CU Boulder Today

SpaceX rocket will be carrying CU experiments – 9NEWS.com

One of the experiments involves cardiovascular stem cells, investigating how gravity affects stem cells.

Jaime Berg, KUSA 4:47 PM. MDT May 31, 2017

Source: University of Colorado

KUSA – A SpaceX rocket is scheduled to launch Thursday — and on board will be two payloads built by researchers at the University of Colorado in Boulder. The payloads include studies that could be life-changing for people on earth.

One of the experiments involves cardiovascular stem cells. The work is with some researchers in California.

Theyre investigating how gravity affects stem cells, including physical and molecular changes. The information, could help lead to stem cell therapies to repair damaged cardiac tissue.

One of the experiments has to do with rodents.

Mice are actually being sent to the international space station, in a NASA habitat, designed for spaceflight.

The mice will be going through a series of experiments to study bone loss in space.

The experiments will be sent in shoebox sized habitats.

Both undergrad and graduate students at CU are involved in the research efforts.

2017 KUSA-TV

Read the original post:
SpaceX rocket will be carrying CU experiments – 9NEWS.com

Curbside Heart Risk; Ear Lobes and Stroke; Heart Pump Recall – MedPage Today

Air pollution, especially from diesel, has again been linked to heart risk, which left researchers suggesting people stay as far from the curb as possible when walking on the sidewalk. (Evening Standard)

Is a diagonal ear lobe crease a signal of stroke risk, or just a surrogate for age? (Daily Mail)

Mechanical thrombectomy for acute ischemic stroke from intracranial occlusion works at least as well for patients with extracranial carotid disease “and it should not be withheld in these complex patients with acute ischemic stroke,” MR CLEAN researchers concluded in the Annals of Internal Medicine.

A faster, cheaper protocol for noninvasive cardiac MRI with contrast tested for use in developing nations appeared feasible and impacted clinical management in 33% of patients, a study reported at EuroCMR in Prague. (EurekAlert press release)

Men may actually suffer more cardiomyopathy from chemotherapy than do women, according to other news from EuroCMR. (Cardiovascular Business)

The HeartMate II heart pump has another controller problem, with a recall following 70 incidents of malfunction when patients attempted to change out the controller on their own, including 26 deaths. Thoratec is shipping new controllers with updated software and hardware, but Mass Device reports that the key thing is for physicians to bring patients into the clinic for controller exchanges.

One lot of ticagrelor (Brilinta) physician samples bottles is being recalled after finding one with an additional medication inside (lesinurad, Zurampic) that could harm the kidneys when taken alone. (FDA MedWatch)

A new orodispersible formulation of ticagrelor (Brilinta, Brilique in Europe) was cleared by European regulators for patients who are intubated or have trouble swallowing conventional tablets. (European Pharmaceutical Review)

A novel robotic arm brace that translates tiny amounts of muscle activity into movement can help patients perform daily activities independently after a stroke, researchers report in the Archives of Physical Medicine and Rehabilitation.

The FDA posted notice of recall of a health supplement (Al-Er-G Capsules from MusclMasster) found to contain the banned substance ephedra, which poses risk of heart attack, stroke, and death.

Normalization of testosterone levels with testosterone replacement therapy was associated with less atrial fibrillation, according to a VA database study in the Journal of the American Heart Association.

A helical transendocardial infusion catheter for cardiac stem cell delivery appeared better for cell retention in a pig model. (International Heart Journal)

Adding chronic kidney disease, measures of systolic blood pressure variability, lupus, and a few other factors to the already extensive list of factors in the QRISK2 algorithm yielded good calibration for 10-year cardiovascular disease risk assessment, but performed about the same as the prior iteration. (BMJ)

Another 15 genes associated with risk for coronary artery disease were described in Nature Genetics.

2017-05-30T12:30:00-0400

See more here:
Curbside Heart Risk; Ear Lobes and Stroke; Heart Pump Recall – MedPage Today

2 Gene Variants Linked to Most Common Congenital Heart Defect – Technology Networks

Researchers are working to determine why the aortic valve doesnt form correctly in patients with the most common congenital heart defect: bicuspid aortic valve.

In a new Nature Communications study, the Michigan Medicine-led group found two genetic variants associated with the condition.

Bicuspid aortic valve is moderately heritable, yet experts are still figuring out which part of our DNA code explains why some BAV patients inherit the disease.

Weve completed the first successful genomewide study of bicuspid aortic valve, by studying subjects at U-Ms Frankel Cardiovascular Center, says first author Bo Yang, M.D., Ph.D., a Michigan Medicine cardiac surgeon. We are using state-of-the-art technology of induced stem cell and gene editing to dissect the genomic region we found to be associated with BAV. Its a great collaboration that will accelerate our scientific understanding of this disease.

BAV patients have aortic valves with only two leaflets, rather than three, limiting the valves function as the heart pumps oxygen-rich blood toward the aorta to enrich the body. The condition is associated with various complications, including a narrowed valve (aortic stenosis), a leaky valve (aortic insufficiency or regurgitation), an infection of the valve or an aortic aneurysm.

“This finding gives us a great head start toward understanding the mechanism of how a genetic change outside the protein-coding part of the genome can lead to disease.”Cristen Willer, Ph.D.

A great head start

The researchers performed genomewide association scans of 466 BAV cases from the Frankel Cardiovascular Center and 4,660 controls from the Michigan Genomics Initiative, with replication on 1,326 cases and 8,103 controls from collaborators at other leading institutions. They also reprogrammed the matured white blood cells to change them back into immortal cells (stem cells) and changed the genetic code of those cells to study the function of the variants they identified through the genomewide association study.

The team reports two genetic variants, both affecting a key cardiac transcription factor called GATA4, reached or nearly reached genomewide significance in BAV. GATA4 is a protein important to cardiovascular development in the womb, and GATA4 mutations have been associated with other cardiovascular defects.

One of the regions we identify actually changes the protein coded by the gene, and the other likely changes expression levels of GATA4 during valve formation, says senior author Cristen Willer, Ph.D., professor of internal medicine, human genetics and computational medicine and bioinformatics. Because most genetic variants associated with human disease are in the 99 percent of the genome that doesnt code for proteins, this finding gives us a great head start toward understanding the mechanism of how a genetic change outside the protein-coding part of the genome can lead to disease.

Specifically, the authors point to a disruption during the endothelial-mesenchymal transition, which is a critical step in the development of the aortic valve. Willer and Yang say this study, with support from the Frankel CVC and the Bob and Ann Aikens Aortic Program, adds new knowledge about the mechanism of BAV formation. They plan to continue to study the biological effect of both variants associated BAV in cells and animal models.

Reference

Yang, B., Zhou, W., Jiao, J., Nielsen, J. B., Mathis, M. R., Heydarpour, M., … & Fritsche, L. (2017). Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve. Nature Communications, 8, 15481.

Read the original:
2 Gene Variants Linked to Most Common Congenital Heart Defect – Technology Networks

Over 40 U.S. National Laboratory Sponsored Experiments on SpaceX CRS-11 Destined for the International Space … – GlobeNewswire (press release)

May 26, 2017 14:28 ET | Source: Center for the Advancement of Science in Space

Kennedy Space Center, FL, May 26, 2017 (GLOBE NEWSWIRE) — The SpaceX Falcon 9 vehicle is slated to launch its 11thcargo resupply mission (CRS-11) to the International Space Station (ISS) no earlier than June 1, 2017 from Kennedy Space Center Launch Complex 39A. Onboard the Falcon 9 launch vehicle is the SpaceX Dragon spacecraft, which will carry more than 40 ISS U.S. National Laboratory sponsored experiments. This mission will showcase the breadth of research possible through the ISS National Laboratory, as experiments range from the life and physical sciences, Earth observation and remote sensing, and a variety of student-led investigations. Below highlights the investigations as part of the SpaceX CRS-11 mission:

ADVANCED COLLOIDS EXPERIMENT-TEMPERATURE CONTROLLED-6 (ACE-T-6)

Matthew Lynch, Procter & Gamble (West Chester, OH)

Implementation Partner: NASA Glenn Research Center and Zin Technologies, Inc.

Colloids are suspensions of microscopic particles in a liquid, and they are found in products ranging from milk to fabric softener. Consumer products often use colloidal gels to distribute specialized ingredients, for instance droplets that soften fabrics, but the gels must serve two opposite purposes: they have to disperse the active ingredient so it can work, yet maintain an even distribution so the product does not spoil. Advanced Colloids Experiment-Temperature-6 (ACE-T-6) studies the microscopic behavior of colloids in gels and creams, providing new insight into fundamental interactions that can improve product shelf life.

EFFICIENCY OF VERMICOMPOSTING IN A CLOSED SYSTEM (NANORACKS-NDC-BMS-VERICOMPOSTING)

Bell Middle School (Golden, CO)

Implementation Partner: NanoRacks

Vermicomposting, or using worms to break down food scraps, is an effective way to reduce waste and obtain a nutrient-rich fertilizer for plants. The NanoRacks-NDC-Bell Middle School-Efficiency of Vermicomposting in a Closed System (NanoRacks-NDC-BMS-Vermicomposting) investigation is a student-designed project that studies whether red wiggler worms, a species of earthworm, are able to produce compost in space. Results are used to study the potential for composting as a form of recycling on future long-duration space missions.

FUNCTIONAL EFFECTS OF SPACEFLIGHT ON CARDIOVASCULAR STEM CELLS (CARDIAC STEM CELLS)

Dr. Mary Kearns-Jonker, Loma Linda University (Loma Linda, CA)

Implementation Partner: BioServe Space Technologies

Functional Effects of Spaceflight on Cardiovascular Stem Cells (Cardiac Stem Cells) investigates how microgravity alters stem cells and the factors that govern stem cell activity, including physical and molecular changes. Spaceflight is known to affect cardiac function and structure, but the biological basis for this is not clearly understood. This investigation helps clarify the role of stem cells in cardiac biology and tissue regeneration. In addition, this research could confirm the hypothesis that microgravity accelerates the aging process.

MULTIPLE USER SYSTEM FOR EARTH SENSING (MUSES)

Paul Galloway, Teledyne Brown Engineering (Huntsville, AL)

Implementation Partner: Teledyne Brown Engineering

Teledyne Brown Engineering developed the Multiple User System for Earth Sensing (MUSES), an Earth imaging platform, as part of the companys new commercial space-based digital imaging business. MUSES hosts earth-viewing instruments (Hosted Payloads), such as high resolution digital cameras, hyperspectral imagers, and provides precision pointing and other accommodations. It hosts up to four instruments at the same time, and offers the ability to

change, upgrade, and robotically service those instruments. It also provides a test bed for technology demonstration and technology maturation by providing long-term access to the space environment on the ISS.

NANORACKS-JAMSS-2LAGRANGE-1

Tomohiro Ichikawa, Lagrange Corp. (Tokyo, Japan)

Implementation Partner: NanoRacks

Spaceflight affects organisms in a wide range of ways, from a reduction in human bone density to changes in plant root growth. NanoRacks-JAMSS-2 Lagrange-1 helps students understand potential spaceflight-related changes by exposing plant seeds to microgravity, and then germinating and growing them on Earth. The plants are compared with specimens grown from seeds that remained on the ground. The investigation also connects students to the space program by sending their photographic likenesses and personal messages into orbit. This connection inspires the next generation of scientists and engineers who will work on international space programs.

NEUTRON CRYSTALLOGRAPHIC STUDIES OF HUMAN ACETYLCHOLINESTERASE FOR THE DESIGN OF ACCERERATED REACTIVATORS (ORNL-PCG)

Dr. Andrey Kovalevsky, Oak Ridge National Laboratory (Oak Ridge, TN)

Implementation Partner: CASIS

The investigative team is trying to improve our understanding of acetylcholinesterase, an enzyme essential for normal communication between nerve cells and between nerve and muscle cells. As a target of deadly neurotoxins produced by animals as venom or by man as nerve agents and pesticides, understanding the structure of acetylcholinesterase is critical to designing better antidotes to poisoning by chemicals that attack the nervous system. The Oak Ridge National Lab team plans to use the microgravity environment of space to grow large crystals of the enzyme that will be imaged back on Earth using a powerful imaging approach called neutron diffraction. Neutron diffraction yields very detailed structural information but requires much larger crystals than traditional x-ray diffraction imaging methods. The investigators hypothesize that structural images of space-grown crystals will bring us closer to more effective and less toxic antidotes for neurotoxins that bind and inhibit acetylcholinesterase.

STUDENT SPACEFLIGHTS EXPERIMENT PROGRAM MISSION 10

Dr. Jeff Goldstein, National Center for Earth and Space Science Education (Washington, D.C.)

Implementation Partner: NanoRacks

The Student Spaceflight Experiments Program (SSEP) provides one of the most exciting educational opportunities available: student-designed experiments to be flown on the International Space Station. The NanoRacks-National Center for Earth and Space Science Education-Odyssey (NanoRacks-NCESSE-Odyssey) investigation contains 24 student experiments, including microgravity studies of plant, algae and bacterial growth; polymers; development of multi-cellular organisms; chemical and physical processes; antibiotic efficacy; and allergic reactions. The program immerses students and teachers in real science, providing first-hand experience conducting scientific experiments and connecting them to the space program.

SYSTEMIC THERAPY OF NELL-1 FOR OSTEOPOROSIS (RODENT RESEARCH-5)

Dr. Chia Soo, University of California at Los Angeles (Los Angeles, CA)

Implementation Partner: NASA Ames Research Center and BioServe Space Technologies

Astronauts living in space for extended durations experience bone density loss, or osteoporosis. Currently, countermeasures include daily exercise designed to prevent bone loss from rapid bone density loss deterioration. However, in space and on Earth, therapies for osteoporosis cannot restore bone that is already lost. The Systemic Therapy of NELL-1 for Osteoporosis (Rodent Research-5) investigation tests a new drug on rodents that can both rebuild bone and block further bone loss, improving health for crew members in orbit and people on Earth. Dr. Soos laboratory has been funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases within the National Institutes of Health. This experiment builds on those previous research investigations.

THE EFFECT OF MICROGRAVITY ON TWO STRAINS OF BIOFUEL PRODUCING ALGAE WITH IMPLICATIONS FOR THE PRODUCTION OF RENEWABLE FUELS IN SPACE-BASED APPLICATIONS

Chatfield High School (Littleton, CO)

Implementation Partner: NanoRacks

Algae can produce both fats and hydrogen, which can each be used as fuel sources on Earth and potentially in space. NanoRacks-National Design Challenge-Chatfield High School-The Effect of Microgravity on Two Strains of Biofuel Producing Algae with Implications for the Production of Renewable Fuels in Space Based Applications (NanoRacks-NDC-CHS-The Green Machine) studies two algae species to determine whether they still produce hydrogen and store fats while growing in microgravity. Results from this student-designed investigation improve efforts to produce a sustainable biofuel in space, as well as remove carbon dioxide from crew quarters.

TOMATOSPHERE-II

Ann Jorss, First the Seed Foundation (Alexandria, VA)

Implementation Partner: CASIS

Tomatosphere is a hands-on student research experience with a standards-based curriculum guide that provides students the opportunity to investigate, create, test, and evaluate a solution for a real world case study. Tomatosphere provides information about how spaceflight affects seed and plant growth and which type of seed is likely to be most suitable for long duration spaceflight. It also exposes students to space research, inspiring the next generation of space explorers. It is particularly valuable in urban school settings where students have little connection to agriculture. In its 15-year existence, the program has reached approximately 3.3 million students.

VALLEY CHRISTIAN HIGH SCHOOL STUDENT EXPERIMENTS

Valley Christian High School (San Jose, CA), in partnership with other high schools throughout the world

Implementation Partner: NanoRacks

Students at Valley Christian High School (VCHS) have a rich history of sending investigations to the ISS through its launch partner, NanoRacks. On SpaceX CRS-11, students from VCHS have partnered with other students from across the world to send 12 total experiments to the ISS National Laboratory. Investigations will range from investigating high quality food nutrients, to the fermentation of microbes, to even an investigation monitoring the growth of a special bacterial strain. The program VCHS has developed with NanoRacks allows students the opportunity to not only conceive a flight project, but learn, understand, and implement the engineering required for a successful experiment in microgravity.

Thus far in 2017, the ISS National Lab has sponsored over 75 separate experiments that have reached the station. This launch manifest adds to an impressive list of experiments from previous missions in 2017 to include; stem cell studies, cell culturing, protein crystal growth, external platform payloads, student experiments, Earth observation and remote sensing. To learn more about those investigations and other station research, visit http://www.spacestationresearch.com.

# # #

About CASIS: The Center for Advancement of Science in Space (CASIS) is the non-profit organization selected to manage the ISS National Laboratory with a focus on enabling a new era of space research to improve life onEarth. In this innovative role, CASIS promotes and brokers a diverse range of research inlife sciences,physical sciences,remote sensing,technology development,andeducation.

Since 2011, the ISS National Lab portfolio has included hundreds of novel research projects spanning multiple scientific disciplines, all with the intention of benefitting life on Earth.. Working together with NASA, CASIS aims to advance the nations leadership in commercial space, pursue groundbreaking science not possible on Earth, and leverage the space station to inspire the next generation.

About the ISS National Laboratory: In 2005, Congress designated the U.S. portion of the International Space Station as the nation’s newest national laboratory to maximize its use for improving life on Earth, promoting collaboration among diverse users, and advancing STEM education. This unique laboratory environment is available for use by other U.S. government agencies and by academic and private institutions, providing access to the permanent microgravity setting, vantage point in low Earth orbit, and varied environments of space.

# # #

Attachments:

http://www.globenewswire.com/NewsRoom/AttachmentNg/d48a20de-af55-4274-8ce8-dd876e62a78d

Attachments:

A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/565f968b-ad65-42c2-be54-97423c9dbcba

Related Articles

Read the original:
Over 40 U.S. National Laboratory Sponsored Experiments on SpaceX CRS-11 Destined for the International Space … – GlobeNewswire (press release)

Dissecting the Press Release for a Failed Stem Cell Trial – MedPage Today

Stem cells have never been shown to have any clinical benefit in patients with heart disease. But there is mounting anecdotal evidence that they may have serious adverse effects on the reasoning and objectivity of the medical researchers, biotechnology executives and investors who get sucked into their orbit.

The most recent example is the ALLSTAR trial, which crashed and burned last week. In a press release, Capricor Therapeutics announced that “a pre-specified administrative interim analysis performed on six-month follow-up data from the ALLSTAR Trial, an ongoing randomized, double-blind, placebo-controlled, 142-patient Phase II clinical trial of CAP-1002 (allogeneic cardiosphere-derived cells) in adults who have experienced a large heart attack with residual cardiac dysfunction, has demonstrated a low probability (futility) of achieving a statistically-significant difference in the 12-month primary efficacy endpoint of percent change from baseline infarct size as a percent of left ventricular mass, measured by cardiac magnetic resonance imaging (MRI).”

But in the press release the trial investigators and company officials never even mention the distinct possibility that their product doesn’t work. Instead, they do everything they can to spin all sorts of positive views of the results.

For instance, co-principal investigator Raj Makkar, of the Cedars-Sinai Heart Institute, is quoted in the press release as saying that “we are disappointed that the ALLSTAR six-month data did not demonstrate evidence of scar size improvement with CAP-1002, given the robust findings demonstrated on this measure in the randomized Phase I CADUCEUS clinical trial of cardiosphere-derived cells in a similar patient population.”

But Makkar conveniently ignores the fact that the earlier trial missed its most important endpoint, improvement in left ventricular ejection fraction and it was on this basis that infarct size was the main goal of ALLSTAR. In other words, infarct size was a cherry picked endpoint in ALLSTAR only because the preferred endpoint didn’t work out in the earlier trial.

In the press release Makkar tries to explain away the failure: “We believe it is important to note that the observed improvements in scar size in the placebo group are markedly inconsistent with the well-established natural history of this disease process. It is certainly possible that, for a variety of reasons, the greater number of sites involved in the conduct of ALLSTAR contributed to an increase in variability seen in the scar measurements as determined by MRI.”

Makkar doesn’t elaborate on any of the “variety of reasons” why “the greater number of sites” leads to the negative finding. In general, in a well conducted trial more sites and more patients should lead to greater reliability of the finding, not less. Makkar appears to be implying that he and his group are the only ones who are able to see the benefits for which they are looking. This should raise all sorts of red flags.

Indeed, everyone quoted in the press release including Makkar has a strong motivation for the therapy to succeed.

First, they are all closely connected. There is not even the pretense of an outside, objective perspective. Linda Marbn is the president and CEO of Capricor. She is also married to Eduardo Marbn, a prominent researcher and the founder of Capricor. Eduardo Marbn is also the director of the Cedars-Sinai Heart Institute. The two co-principal investigators of ALLSTAR are Makkar and Timothy Henry, both of whom work under Marbn at Cedars Sinai. Makkar is the associate director of interventional technologies in the Heart Institute and Henry heads the division of cardiology.

The conflicts are even more deep rooted. The home institution for Marbn and the other investigators, Cedars-Sinai, has a significant financial stake in Capricor.

Henry also sought and found positive signs in the trial. “We are encouraged to see reductions in left ventricular volume measures in the CAP-1002 treated patients, an important indicator of reverse remodeling of the heart. These findings support the biological activity of CAP-1002.” But when you miss your major prespecified endpoint any secondary findings must be considered exploratory at best. Given the dismal results of all previous stem cell trials in cardiology extreme skepticism is warranted in this sort of analysis. But Henry, a veteran stem cell researcher, doesn’t express any such caution.

Everyone involved is highly motivated to see this as a success. They all have rose-tinted glasses. Who among any of these major players has any motivation to view the company, the products, or the underlying science objectively or critically?

This is the nearly inevitable danger when there’s no outside critical perspective, and it is especially dangerous in small studies without rigorous controls. The investigators are motivated to grasp at the straws, which in this case means cherry picking their endpoints.

A New Target

Despite the optimistic spin, in its press release the company indicated it would likely abandon the cardiac indication for CAP-1002 in favor of a new indication in boys and young men with Duchenne muscular dystrophy (DMD). The company recently reported positive interim information from a 25-patient phase I/II trial in this population.

“Although we are disappointed, the favorable safety profile demonstrated by CAP-1002 in ALLSTAR supports the prospect of its chronic, repeat administration in patients with Duchenne muscular dystrophy. Also, the potent anti-inflammatory properties of CAP-1002 may be well-suited to mitigate DMD progression, for which chronic inflammation is believed to play a causative role,” said Linda Marbn.

Given the history, of this therapy in particular and of stem cells in general, extreme caution is warranted.

An important motivating factor for Capricor may well be that the regulatory barrier is much lower for a DMD indication than for a cardiac indication, as demonstrated last year by the approval of Sarepta’s DMD drug with little or no evidence of clinical benefit. Capricor plans to ask the FDA to grant Breakthrough Therapy or Regenerative Medicine Advanced Technology status for the new CAP-1002 indication.

A String of Failures

Hundreds of millions of dollars have been spent on cardiac stem cell research over nearly two decades now without any sign of success or progress.

Recently, as reported by Retraction Watch, in the latest installment of a long-running scandal, Brigham and Women’s Hospital agreed to give back $10 million to the US government in response to fraud charges against 3 prominent stem cell researchers, Piero Anversa, Annarosa Leri, and Jan Kajstura. Anversa, it should be noted, practically invented the field of cardiac stem cell therapy when he first reported that cardiac cells were capable of regeneration.

I recently criticized another prominent leader in the field, Roberto Bolli, for arguing that the proper response to this dismal record is more stem cell therapy, not less. With absolutely no concrete evidence, he argued that the single dose of cells used in virtually all previous stem cell therapy trials should be replaced with repeated doses of stem cells.

ALLSTAR is only the latest in a string of failures for stem cell therapies. Isn’t it time for people in the field to acknowledge that after decades of failure the field is not going to move forward?

Previous Stem Cell Stories:

2017-05-22T14:00:00-0400

See the original post:
Dissecting the Press Release for a Failed Stem Cell Trial – MedPage Today

Heart Disease | Harvard Stem Cell Institute (HSCI)

The Harvard Stem Cell Institute is developing new techniques to grow and transplant heart cells, replacing those lost to cardiovascular disease.

The greatest threat to the long-term health and well-being of people living with diabetes is cardiovascular disease. The diabetic population as a whole is two to four times more likely than non-diabetics to develop heart disease or suffer a stroke. Type 1 diabetes, which is most often diagnosed in childhood and adolescence, is particularly devastating, as one New England Journal of Medicine study associated it with a ten-fold increase in cardiovascular disease.

The human adult heart has about five billion heart cells, all pulsing as a coordinated orchestra with every heartbeat. These cells can be killed by high blood pressure, blood clots, heart attacks, and other byproducts of cardiovascular disease. The heart has an age-related block in its ability to make new heart cells, so that damaged cells are not replaced in the latter half of life, precisely when we need them the most. A typical patient with heart failure has lost over a billion heart cells.

Harvard Stem Cell Institute (HSCI) investigators are developing ways to make replacement heart cells and provide them with the right cues so that the new cells play as needed in the orchestra.

Both embryonic stem cells and induced pluripotent stem cells mature cells that are manipulated back to a stem cell state can be harnessed to create new heart cells. The difficulty is that the heart cells made with stem cells resemble the heart cells of an infant, rather than adult heart cells. To function in adult hearts, the new heart cells must mature and then be able to survive within the constantly beating environment of the heart.

The scientific community has generated the technology to make heart cells that are immature, but very few heart cells derived from stem cells integrate into the normal heart tissue as mature heart cells. At the HSCI, our researchers are focused on understanding how to take these new heart cells all the way to maturity and stability, so they can be used as an effective therapy.

HSCI scientists are also developing ways of using the bodys heart matrix the rich, intricate scaffold of the heart that serves as the permanent home for our heart cells to guide maturation and prolong the survival of heart cells derived from stem cells after implantation.

The heart matrix is like the sheet music for the heart orchestra. It tells the heart cells where to sit and how to function with their neighbors so that a heartbeat is in sync. The problem of redrawing these matrix-directed instructions from scratch once seemed too daunting to tackle.

By breaking down the hearts scaffold material into thousands of individual chemicals, HSCI researchers hope to rebuild the environments that allow immature heart cells to mature. Armed with this knowledge, it will be possible to construct real adult heart tissue in the laboratory, as well as realistic approaches to transplanting patient-specific heart cells into their damaged organs.

In addition to these ambitious projects, HSCI is pursuing interim objectives before reaching the ultimate goal of reconstructing the heart. For example, a recent study led to the identification of a blood circulating factor that declines with age but, when injected, can reverse age-related heart enlargement and accompanying heart failure. If this is successful in human studies, we will have identified a new therapeutic approach for the aging heart.

Read more:
Heart Disease | Harvard Stem Cell Institute (HSCI)

Miltenyi Biotec Showcases the Generation of Purified Human iPSC Derived Cardiomyocytes – PR Web (press release)

Todd J. Herron, BS, PhD Director of the Frankel Cardiovascular Center’s Cardiovascular Regeneration Core Laboratory and Assistant Research Professor at the University of Michigan Center for Arrhythmia

Yorba Linda, Ca (PRWEB) May 23, 2017

Pluripotent stem cells (PSCs) offer an unlimited source of human cardiovascular cells for research and the development of cardiac regeneration therapies. The development of highly efficient cardiac-directed differentiation methods makes it possible to generate large numbers of cardiomyocytes (hPSC-CMs). Due to varying differentiation efficiencies, further enrichment of CM populations for downstream applications is essential.

Recently, a CM-specific cell surface marker called SIRPa (signal-regulatory protein alpha, also termed CD172a) was reported to be a useful tool for flow sorting of human stem cellderived CMs. However, our expression analysis revealed that SIRPa only labels a subpopulation of CMs indicated by cardiac Troponin T (cTnT) expression. Moreover, SIRPa is also expressed on a sub population of non-CMs, hence making SIRa an inadequate marker to enrich PSC-derived CMs.

In this webinar, sponsored by the team at Miltenyi Biotec, participants will have a chance to review human induced pluripotent stem cell derivation, cardiac directed differentiation to human pluripotent stem cell cardiomyocytes (hPSC-CMs), enrichment of hPSC-CMs and subsequent formation of 2D monolayers of electrically connected cells. They will also learn of the generation of purified human induced pluripotent stem cell derived cardiomyocyte.

The speaker for this event will be Dr. Todd J. Herron, director of the Frankel Cardiovascular Center’s Cardiovascular Regeneration Core Laboratory and Assistant Research Professor at the University of Michigan Center for Arrhythmia Research.

Herron currently serves as the director of the Frankel Cardiovascular Center’s Cardiovascular Regeneration Core Laboratory, as well as holding a position on the faculty in the University of Michigan Medical School and has appointments in the Department of Internal Medicine and Molecular & Integrative Physiology as Associate Research Scientist. His research is focused on the complex interplay between cardiac electrical excitation and contractile force generation-a process known classically as excitation-contraction coupling.

LabRoots will host the event June 7, 2017, beginning at 9 a.m. PDT, 12 p.m. EDT. To read more about this event, learn about the continuing education credits offered, or to register for free, click here.

ABOUT MILTENYI BIOTEC Miltenyi Biotec is a global provider of products and services that advance biomedical research and cellular therapy. The companys innovative tools support research at every level, from basic research to translational research to clinical application. This integrated portfolio enables scientists and clinicians to obtain, analyze, and utilize the cell. Miltenyi Biotecs technologies cover techniques of sample preparation, cell isolation, cell sorting, flow cytometry, cell culture, molecular analysis, and preclinical imaging. Their more than 25 years of expertise spans research areas including immunology, stem cell biology, neuroscience, and cancer, and clinical research areas like hematology, graft engineering, and apheresis. In their commitment to the scientific community, Miltenyi Biotec also offers comprehensive scientific support, consultation, and expert training. Today, Miltenyi Biotec has more than 1,500 employees in 25 countries all dedicated to helping researchers and clinicians around the world make a greater impact on science and health.

ABOUT LABROOTS LabRoots is the leading scientific social networking website, which provides daily scientific trending news and science-themed apparel, as well as produces educational virtual events and webinars, on the latest discoveries and advancements in science. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the worlds largest series of virtual events within the Life Sciences and Clinical Diagnostics community.

Share article on social media or email:

Here is the original post:
Miltenyi Biotec Showcases the Generation of Purified Human iPSC Derived Cardiomyocytes – PR Web (press release)

Robot hearts: medicine’s new frontier – The Guardian

On a cold, bright January morning I walked south across Westminster Bridge to St Thomas Hospital, an institution with a proud tradition of innovation: I was there to observe a procedure generally regarded as the greatest advance in cardiac surgery since the turn of the millennium and one that can be performed without a surgeon.

The patient was a man in his 80s with aortic stenosis, a narrowed valve which was restricting outflow from the left ventricle into the aorta. His heart struggled to pump sufficient blood through the reduced aperture, and the muscle of the affected ventricle had thickened as the organ tried to compensate. If left unchecked, this would eventually lead to heart failure. For a healthier patient the solution would be simple: an operation to remove the diseased valve and replace it with a prosthesis. But the mans age and a long list of other medical conditions made open-heart surgery out of the question. Happily, for the last few years, another option has been available for such high-risk patients: transcatheter aortic valve implantation, known as TAVI for short.

This is a non-invasive procedure, and takes place not in an operating theatre but in the catheterisation laboratory, known as the cath lab. When I got there, wearing a heavy lead gown to protect me from X-rays, the patient was already lying on the table. He would remain awake throughout the procedure, receiving only a sedative and a powerful analgesic. I was shown the valve to be implanted, three leaflets fashioned from bovine pericardium (a tough membrane from around the heart of a cow), fixed inside a collapsible metal stent. After being soaked in saline it was crimped on to a balloon catheter and squeezed, from the size and shape of a lipstick, into a long, thin object like a pencil.

The consultant cardiologist, Bernard Prendergast, had already threaded a guidewire through an incision in the patients groin, entering the femoral artery and then the aorta, until the tip of the wire had arrived at the diseased aortic valve. The catheter, with its precious cargo, was then placed over the guidewire and pushed gently up the aorta. When it reached the upper part of the vessel we could track its progress on one of the large X-ray screens above the table. We watched intently as the metal stent described a slow curve around the aortic arch before coming to rest just above the heart.

There was a pause as the team checked everything was ready, while on the screen the silhouette of the furled valve oscillated gently as it was buffeted by pulses of high-pressure arterial blood. When Prendergast was satisfied that the catheter was precisely aligned with the aortic valve, he pressed a button to inflate the tiny balloon. As it expanded it forced the metal stent outwards and back to its normal diameter, and on the X-ray monitor it suddenly snapped into position, firmly anchored at the top of the ventricle. For a second or two the patient became agitated as the balloon obstructed the aorta and stopped the flow of blood to his brain; but as soon as it was deflated he became calm again.

Prendergast and his colleagues peered at the monitors to check the positioning of the device. In a conventional operation the diseased valve would be excised before the prosthesis was sewn in; during a TAVI procedure the old valve is left untouched and the new one simply placed inside it. This makes correct placement vital, since unless the device fits snugly there may be a leak around its edge. The X-ray picture showed that the new valve was securely anchored and moving in unison with the heart. Satisfied that everything had gone according to plan, Prendergast removed the catheter and announced the good news in a voice that was probably audible on the other side of the river. Just minutes after being given a new heart valve, the patient raised an arm from under the drapes and shook the cardiologists hand warmly. The entire procedure had taken less than an hour.

According to many experts, this is what the future will look like. Though available for little more than a decade, TAVI is already having a dramatic impact on surgical practice: in Germany the majority of aortic valve replacements, more than 10,000 a year, are now performed using the catheter rather than the scalpel.

In the UK, the figure is much lower, since the procedure is still significantly more expensive than surgery this is largely down to the cost of the valve itself, which can be as much as 20,000 for a single device. But as the manufacturers recoup their initial outlay on research and development, it is likely to become more affordable and its advantages are numerous. Early results suggest that it is every bit as effective as open-heart surgery, without many of surgerys undesirable aspects: the large chest incision, the heart-lung machine, the long period of post-operative recovery.

The essential idea of TAVI was first suggested more than half a century ago. In 1965, Hywel Davies, a cardiologist at Guys Hospital in London, was mulling over the problem of aortic regurgitation, in which blood flows backwards from the aorta into the heart. He was looking for a short-term therapy for patients too sick for immediate surgery something that would allow them to recover for a few days or weeks, until they were strong enough to undergo an operation. He hit upon the idea of a temporary device that could be inserted through a blood vessel, and designed a simple artificial valve resembling a conical parachute. Because it was made from fabric, it could be collapsed and mounted on to a catheter. It was inserted with the top of the parachute uppermost, so that any backwards flow would be caught by its inside surface like air hitting the underside of a real parachute canopy. As the fabric filled with blood it would balloon outwards, sealing the vessel and stopping most of the anomalous blood flow.

This was a truly imaginative suggestion, made at a time when catheter therapies had barely been conceived of, let alone tested. But, in tests on dogs, Davies found that his prototype tended to provoke blood clots and he was never able to use it on a patient.

Another two decades passed before anybody considered anything similar. That moment came in 1988, when a trainee cardiologist from Denmark, Henning Rud Andersen, was at a conference in Arizona, attending a lecture about coronary artery stenting. It was the first he had heard of the technique, which at the time had been used in only a few dozen patients, and as he sat in the auditorium he had a thought, which at first he dismissed as ridiculous: why not make a bigger stent, put a valve in the middle of it, and implant it into the heart via a catheter? On reflection, he realised that this was not such an absurd idea, and when he returned home to Denmark he visited a local butcher to buy a supply of pig hearts. Working in a pokey room in the basement of his hospital with basic tools obtained from a local DIY warehouse, Andersen constructed his first experimental prototypes. He began by cutting out the aortic valves from the pig hearts, mounted each inside a home-made metal lattice then compressed the whole contraption around a balloon.

Within a few months Andersen was ready to test the device in animals, and on 1 May 1989 he implanted the first in a pig. It thrived with its prosthesis, and Andersen assumed that his colleagues would be excited by his works obvious clinical potential. But nobody was prepared to take the concept seriously folding up a valve and then unfurling it inside the heart seemed wilfully eccentric and it took him several years to find a journal willing to publish his research.

When his paper was finally published in 1992, none of the major biotechnology firms showed any interest in developing the device. Andersens crazy idea worked, but still it sank without trace.

Andersen sold his patent and moved on to other things. But at the turn of the century there was a sudden explosion of interest in the idea of valve implantation via catheter. In 2000, a heart specialist in London, Philipp Bonhoeffer, replaced the diseased pulmonary valve of a 12-year-old boy, using a valve taken from a cows jugular vein, which had been mounted in a stent and put in position using a balloon catheter.

In France, another cardiologist was already working on doing the same for the aortic valve. Alain Cribier had been developing novel catheter therapies for years; it was his company that bought Andersens patent in 1995, and Cribier had persisted with the idea even after one potential investor told him that TAVI was the most stupid project ever heard of.

Eventually, Cribier managed to raise the necessary funds for development and long-term testing, and by 2000 had a working prototype. Rather than use an entire valve cut from a dead heart, as Andersen had, Cribier built one from bovine pericardium, mounted in a collapsible stainless-steel stent. Prototypes were implanted in sheep to test their durability: after two-and-a-half years, during which they opened and closed more than 100m times, the valves still worked perfectly.

Cribier was ready to test the device in humans, but his first patient could not be eligible for conventional surgical valve replacement, which is safe and highly effective: to test an unproven new procedure on such a patient would be to expose them to unnecessary risk.

In early 2002, he was introduced to a 57-year-old man who was, in surgical terms, a hopeless case. He had catastrophic aortic stenosis which had so weakened his heart that with each stroke it could pump less than a quarter of the normal volume of blood; in addition, the blood vessels of his extremities were ravaged by atherosclerosis, and he had chronic pancreatitis and lung cancer. Several surgeons had declined to operate on him, and his referral to Cribiers clinic in Rouen was a final roll of the dice. An initial attempt to open the stenotic valve using a simple balloon catheter failed, and a week after this treatment Cribier recorded in his notes that his patient was near death, with his heart barely functioning. The mans family agreed that an experimental treatment was preferable to none at all, and on 16 April he became the first person to receive a new aortic valve without open-heart surgery.

Over the next couple of days the patients condition improved dramatically: he was able to get out of bed, and the signs of heart failure began to retreat. But shortly afterwards complications arose, most seriously a deterioration in the condition of the blood vessels in his right leg, which had to be amputated 10 weeks later. Infection set in, and four months after the operation, he died.

He had not lived long nobody expected him to but the episode had proved the feasibility of the approach, with clear short-term benefit to the patient. When Cribier presented a video of the operation to colleagues they sat in stupefied silence, realising that they were watching something that would change the nature of heart surgery.

When surgeons and cardiologists overcame their initial scepticism about TAVI they quickly realised that it opened up a vista of exciting new surgical possibilities. As well as replacing diseased valves it is now also possible to repair them, using clever imitations of the techniques used by surgeons. The technology is still in its infancy, but many experts believe that this will eventually become the default option for valvular disease, making surgery increasingly rare.

While TAVI is impressive, there is one even more spectacular example of the capabilities of the catheter. Paediatric cardiologists at a few specialist centres have recently started using it to break the last taboo of heart surgery operating on an unborn child. Nowhere is the progress of cardiac surgery more stunning than in the field of congenital heart disease. Malformations of the heart are the most common form of birth defect, with as many as 5% of all babies born with some sort of cardiac anomaly though most of these will cause no serious, lasting problems. The heart is especially prone to abnormal development in the womb, with a myriad of possible ways in which its structures can be distorted or transposed. Over several decades, specialists have managed to find ways of taming most; but one that remains a significant challenge to even the best surgeon is hypoplastic left heart syndrome (HLHS), in which the entire left side of the heart fails to develop properly. The ventricle and aorta are much smaller than they should be, and the mitral valve is either absent or undersized. Until the early 1980s this was a defect that killed babies within days of birth, but a sequence of complex palliative operations now makes it possible for many to live into adulthood.

Because their left ventricle is incapable of propelling oxygenated blood into the body, babies born with HLHS can only survive if there is some communication between the pulmonary and systemic circulations, allowing the right ventricle to pump blood both to the lungs and to the rest of the body. Some children with HLHS also have an atrial septal defect (ASD), a persistent hole in the tissue between the atria of the heart which improves their chances of survival by increasing the amount of oxygenated blood that reaches the sole functioning pumping chamber. When surgeons realised that this defect conferred a survival benefit in babies with HLHS, they began to create one artificially in those with an intact septum, usually a few hours after birth. But it was already too late: elevated blood pressure was causing permanent damage to the delicate vessels of the lungs while these babies still in the womb.

The logical albeit risky response was to intervene even earlier. In 2000, a team at Boston Childrens Hospital adopted a new procedure to create an ASD during the final trimester of pregnancy: they would deliberately create one heart defect in order to treat another. A needle was passed through the wall of the uterus and into the babys heart, and a balloon catheter used to create a hole between the left and right atria. This reduced the pressures in the pulmonary circulation and hence limited the damage to the lungs; but the tissues of a growing foetus have a remarkable ability to repair themselves, and the artificially created hole would often heal within a few weeks. Cardiologists needed to find a way of keeping it open until birth, when surgeons would be able to perform a more comprehensive repair.

In September 2005 a couple from Virginia, Angela and Jay VanDerwerken, visited their local hospital for a routine antenatal scan. They were devastated to learn that their unborn child had HLHS, and the prognosis was poor. The ultrasound pictures revealed an intact septum, making it likely that even before birth her lungs would be damaged beyond repair. They were told that they could either terminate the pregnancy or accept that their daughter would have to undergo open-heart surgery within hours of her birth, with only a 20% chance that she would survive.

Devastated, the VanDerwerkens returned home, where Angela researched the condition online. Although few hospitals offered any treatment for HLHS, she found several references to the Boston foetal cardiac intervention programme, the team of doctors that had pioneered the use of the balloon catheter during pregnancy.

They arranged an appointment with Wayne Tworetzky, the director of foetal cardiology at Boston Childrens Hospital, who performed a scan and confirmed that their unborn childs condition was treatable. A greying, softly spoken South African, Tworetzky explained that his team had recently developed a new procedure, but that it had never been tested on a patient. It would mean not just making a hole in the septum, but also inserting a device to prevent it from closing. The VanDerwerkens had few qualms about accepting the opportunity: the alternatives gave their daughter a negligible chance of life.

The procedure took place at Brigham and Womens Hospital in Boston on 7 November 2005, 30 weeks into the pregnancy, in a crowded operating theatre. Sixteen doctors, with a range of specialisms, took part: cardiologists, surgeons, and four anaesthetists two to look after the mother, two for her unborn child. Mother and child needed to be completely immobilised during a delicate procedure lasting several hours, so both were given a general anaesthetic. The team watched on the screen of an ultrasound scanner as a thin needle was guided through the wall of the uterus, then the foetuss chest and finally into her heart an object the size of a grape.

A guidewire was placed in the cardiac chambers, then a tiny balloon catheter was inserted and used to create an opening in the atrial septum. This had all been done before; but now the cardiologists added a refinement. The balloon was withdrawn, then returned to the heart, this time loaded with a 2.5 millimetre stent that was set in the opening between the left and right atria. There was a charged silence as the balloon was inflated to expand the stent; then, as the team saw on the monitor that blood was flowing freely through the aperture, the room erupted in cheers.

Grace VanDerwerken was born in early January after a normal labour, and shortly afterwards underwent open-heart surgery. After a fortnight she was allowed home, her healthy pink complexion proving that the interventions had succeeded in producing a functional circulation.

But just when she seemed to be out of danger, Grace died suddenly at the age of 36 days not as a consequence of the surgery, but from a rare arrhythmia, a complication of HLHS that occurs in just 5%. This was the cruellest luck, when she had seemingly overcome the grim odds against her. Her death was a tragic loss, but her parents courage had brought about a new era in foetal surgery.

Much of the most exciting contemporary research focuses on the greatest, most fundamental cardiac question of all: what can the surgeon do about the failing heart? Half a century after Christiaan Barnard performed the first human heart transplant, transplantation remains the gold standard of care for patients in irreversible heart failure once drugs have ceased to be effective. It is an excellent operation, too, with patients surviving an average of 15 years. But it will never be the panacea that many predicted, because there just arent enough donor hearts to go round.

With too few organs available, surgeons have had to think laterally. As a result, a new generation of artificial hearts is now in development. Several companies are now working on artificial hearts with tiny rotary electrical motors. In addition to being much smaller and more efficient than pneumatic pumps, these devices are far more durable, since the rotors that impel the blood are suspended magnetically and are not subject to the wear and tear caused by friction. Animal trials have shown promising results, but, as yet, none of these have been implanted in a patient.

Another type of total artificial heart, as such devices are known, has, however, recently been tested in humans. Alain Carpentier, an eminent French surgeon still active in his ninth decade, has collaborated with engineers from the French aeronautical firm Airbus to design a pulsatile, hydraulically powered device whose unique feature is the use of bioprosthetic materials both organic and synthetic matter. Unlike earlier artificial hearts, its design mimics the shape of the natural organ; the internal surfaces are lined with preserved bovine pericardial tissue, a biological surface far kinder to the red blood cells than the polymers previously used. Carpentiers artificial heart was first implanted in December 2013. Although the first four patients have since died two following component failures the results were encouraging, and a larger clinical trial is now under way.

One drawback to the artificial heart still leads many surgeons to dismiss the entire concept out of hand: the price tag. These high-precision devices cost in excess of 100,000 each, and no healthcare service in the world, publicly or privately funded, could afford to provide them to everybody in need of one. And there is one still more tantalising notion: that we will one day be able to engineer spare parts for the heart, or even an entire organ, in the laboratory.

In the 1980s, surgeons began to fabricate artificial skin for burns patients, seeding sheets of collagen or polymer with specialised cells in the hope that they would multiply and form a skin-like protective layer. But researchers had loftier ambitions, and a new field tissue engineering began to emerge.

High on the list of priorities for tissue engineers was the creation of artificial blood vessels, which would have applications across the full range of surgical specialisms. In 1999 surgeons in Tokyo performed a remarkable operation in which they gave a four-year-old girl a new artery grown from cells taken from elsewhere in her body. She had been born with a rare congenital defect which had completely obliterated the right branch of her pulmonary artery, the vessel conveying blood to the right lung. A short section of vein was excised from her leg, and cells from its inside wall were removed in the laboratory. They were then left to multiply in a bioreactor, a vessel that bathed them in a warm nutrient broth, simulating conditions inside the body.

After eight weeks, they had increased in number to more than 12m, and were used to seed the inside of a polymer tube which functioned as a scaffold for the new vessel. The tissue was allowed to continue growing for 10 days, and then the graft was transplanted. Two months later the polymer scaffold around the tissue, designed to break down inside the body, had completely dissolved, leaving only new tissue that would it was hoped grow with the patient.

At the turn of the millennium, a new world of possibility opened up when researchers gained a powerful new tool: stem cell technology. Stem cells are not specialised to one function but have the potential to develop into many different tissue types. One type of stem cell is found in growing embryos, and another in parts of the adult body, including the bone marrow (where they generate the cells of the blood and immune system) and skin. In 1998 James Thomson, a biologist at the University of Wisconsin, succeeded in isolating stem cells from human embryos and growing them in the laboratory.

But an arguably even more important breakthrough came nine years later, when Shinya Yamanaka, a researcher at Kyoto University, showed that it was possible to genetically reprogram skin cells and convert them into stem cells. The implications were enormous. In theory, it would now be possible to harvest mature, specialised cells from a patient, reprogram them as stem cells, then choose which type of tissue they would become.

Sanjay Sinha, a cardiologist at the University of Cambridge, is attempting to grow a patch of artificial myocardium (heart muscle tissue) in the laboratory for later implantation in the operating theatre. His technique starts with undifferentiated stem cells, which are then encouraged to develop into several types of specialised cell. These are then seeded on to a scaffold made from collagen, a tough protein found in connective tissue. The presence of several different cell types means that when they have had time to proliferate, the new tissue will develop its own blood supply.

Clinical trials are still some years away, but Sinha hopes that one day it will be possible to repair a damaged heart by sewing one of these patches over areas of muscle scarred by a heart attack.

Using advanced tissue-engineering techniques, researchers have already succeeded in creating replacement valves from the patients own tissue. This can be done by harvesting cells from elsewhere in the body (usually the blood vessels) and breeding them in a bioreactor, before seeding them on to a biodegradable polymer scaffold designed in the shape of a valve. Once the cells are in place they are allowed to proliferate before implantation, after which the scaffold melts away, leaving nothing but new tissue. The one major disadvantage of this approach is that each valve has to be tailor-made for a specific patient, a process that takes weeks. In the last couple of years, a group in Berlin has refined the process by tissue-engineering a valve and then stripping it of cellular material, leaving behind just the extracellular matrix the structure that holds the cells in position.

The end result is therefore not quite a valve, but a skeleton on which the body lays down new tissue. Valves manufactured in this way can be implanted, via catheter, in anybody; moreover, unlike conventional prosthetic devices, if the recipient is a child the new valve should grow with them.

If it is possible to tissue-engineer a valve, then why not an entire heart? For many researchers this has come to be the ultimate prize, and the idea is not necessarily as fanciful as it first appears.

In 2008, a team led by Doris Taylor, a scientist at the University of Minnesota, announced the creation of the worlds first bioartificial heart composed of both living and manufactured parts. They began by pumping detergents through hearts excised from rats. This removed all the cellular tissue from them, leaving a ghostly heart-shaped skeleton of extracellular matrix and connective fibre, which was used as a scaffold onto which cardiac or blood-vessel cells were seeded. The organ was then cultured in a bioreactor to encourage cell multiplication, with blood constantly perfused through the coronary arteries. After four days, it was possible to see the new tissue contracting, and after a week the heart was even capable of pumping blood though only 2% of its normal volume.

This was a brilliant achievement, but scaling the procedure up to generate a human-sized heart is made far more difficult by the much greater number of cells required. Surgeons in Heidelberg have since applied similar techniques to generate a human-sized cardiac scaffold covered in living tissue. The original heart came from a pig, and after it had been decellularised it was populated with human vascular cells and cardiac cells harvested from a newborn rat. After 10 days the walls of the organ had become lined with new myocardium which even showed signs of electrical activity. As a proof of concept, the experiment was a success, though after three weeks of culture the organ could neither contract nor pump blood.

Growing tissues and organs in a bioreactor is a laborious business, but recent improvements in 3D printing offer the tantalising possibility of manufacturing a new heart rapidly and to order. 3D printers work by breaking down a three-dimensional object into a series of thin, two-dimensional slices, which are laid down one on top of another. The technology has already been employed to manufacture complex engineering components out of metal or plastic, but it is now being used to generate tissues in the laboratory. To make an aortic valve, researchers at Cornell University took a pigs valve and X-rayed it in a high-resolution CT scanner. This gave them a precise map of its internal structure which could be used as a template. Using the data from the scan, the printer extruded thin jets of a hydrogel, a water-absorbent polymer that mimics natural tissue, gradually building up a duplicate of the pig valve layer by layer. This scaffold could then be seeded with living cells and incubated in the normal way.

Pushing the technology further, Adam Feinberg, a materials scientist at Carnegie Mellon University in Pittsburgh, recently succeeded in fabricating the first anatomically accurate 3D-printed heart. This facsimile was made of hydrogel and contained no tissue, but it did show a remarkable fidelity to the original organ. Since then, Feinberg has used natural proteins such as fibrin and collagen to 3D-print hearts. For many researchers in this field, a fully tissue-engineered heart is the ultimate prize.

We are left with several competing visions of the future. Within a few decades it is possible that we will be breeding transgenic pigs in vast sterile farms and harvesting their hearts to implant in sick patients. Or that new organs will be 3D-printed to order in factories, before being dispatched in drones to wherever they are needed. Or maybe an unexpected breakthrough in energy technology will make it possible to develop a fully implantable, permanent mechanical heart.

Whatever the future holds, it is worth reflecting on how much has been achieved in so little time. Speaking in 1902, six years after Ludwig Rehn became the first person to perform cardiac surgery, Harry Sherman remarked that the road to the heart is only two or three centimetres in a direct line, but it has taken surgery nearly 2,400 years to travel it. Overcoming centuries of cultural and medical prejudice required a degree of courage and vision still difficult to appreciate today. Even after that first step had been taken, another 50 years elapsed before surgeons began to make any real progress. Then, in a dizzying period of three decades, they learned how to open the heart, repair and even replace it. In most fields, an era of such fundamental discoveries happens only once if at all and it is unlikely that cardiac surgeons will ever again captivate the world as Christiaan Barnard and his colleagues did in 1967. But the history of heart surgery is littered with breakthroughs nobody saw coming, and as long as there are surgeons of talent and imagination, and a determination to do better for their patients, there is every chance that they will continue to surprise us.

Main photograph: Getty Images

This is an adapted extract from The Matter of the Heart by Thomas Morris, published by the Bodley Head

Follow the Long Read on Twitter at @gdnlongread, or sign up to the long read weekly email here.

Continued here:
Robot hearts: medicine’s new frontier – The Guardian

AHA awards $2 million to cardiac research at top universities – Cardiovascular Business

The American Heart Association (AHA) announced May 19 that it will donate two $1 million research grants to support research on medications and high blood pressure.

The money will be awarded over five years to Stanford University and the University of Pennsylvania, according to a statement from the AHA.

[These] competitive research programs are pushing the boundaries of their respective disciplines by undertaking high-risk projects whose outcomes could revolutionize the treatment for new classes of blood pressure medications and our approaches for clinical trials in the era of precision medicine, said Ivor Benjamin, MD, who chairs the AHAs research committee.

Joseph Wu, MD, the director of theStanford Cardiovascular Institute at Stanford University School of Medicine, is leading the research on medication. He plans to use information from stem cells to speed up the slow and expensive process of introducing a new drug to the market.

Our project has tremendous potential significance for testing new drugs very efficiently compared to the traditional drug screening that the pharmaceutical industry has to go througha process that has stagnated and become almost too costly to help patients, Wu said.

The second research project, spearheaded by Garret FitzGerald, MD, a professor of medicine and systems pharmacology and translational therapeutics at the University of Pennsylvanias Perelman School of Medicine, aims to improve blood pressure control over a 24-hour period.

Given the increasing prevalence of high blood pressure in our aging population and in the developing world generally, this program promises to have a considerable impact on global health, FitzGerald said.

Read the rest here:
AHA awards $2 million to cardiac research at top universities – Cardiovascular Business

Researchers show cancer drug class has cardiac benefits – BioWorld Online

By Anette Breindl Senior Science Editor

“With the advent of targeted cancer therapies, what we’ve found is that many of them are cardiotoxic,” Saptarsi Haldar told BioWorld Today. “Pathways that are effective in cancer are toxic in the heart.”

In the May 17, 2017, issue of Science Translational Medicine, Haldar, who is an associate investigator at the Gladstone Institute of Cardiovascular Disease, and his colleagues showed that a class of epigenetic drugs, the BET bromodomain inhibitors, may be not just an exception to that rule, but a class of drugs that has therapeutic utility in heart failure.

The team showed that the bromodomain inhibitor JQ-1 had therapeutic benefits in two separate animal models of advanced heart failure, but did not affect the beneficial changes to heart muscle cells that are a consequence of exercise.

The paper shows a potential new approach to heart failure an indication that, with a five-year survival rate of 60 percent, needs them.

It also shows a potential approach to another vexing problem, namely drugging transcription factors.

“There’s a surprisingly tractable therapeutic index for drugging transcription in diseases,” Haldar said.

While BRD4 is not itself a transcription factor, inhibiting it “dampens the transcription factor-driven network that’s driving the disease . . . This is really about dampening transcriptional rewiring,” he added.

In heart failure, those happen to be innate immune signaling and fibrotic signaling. Experiments in cardiac cells derived from induced pluripotent stem cells (iPSCs) showed that JQ-1 acted by blocking the activation of innate immune and profibrotic pathways, essentially preventing heart cells from rewiring themselves in maladaptive ways in response to being chronically overworked.

Haldar said the original idea to test whether the compound would have an effect in heart failure was based on “an educated guess.”

Previous work had shown that certain epigenetic marks, namely acetyl marks on lysines, play a role in heart failure.

“There is a lot known about lysine acetylation in heart failure,” Haldar said, and there had been previous attempts at targeting the process, which had “fallen to the wayside, in part because of issues with therapeutic index.”

Even studying the molecular details of lysine acetylation’s role in heart failure was challenging, because genetic approaches are not viable.

The problem became tractable with the synthesis of JQ-1 in the laboratory of James Bradner, who is a co-author on the Science Translational Medicine paper. The compound, which has been used to gain insight into epigenetic aspects of a large number of biological processes thanks to the decision of its developers to distribute it freely, targets BRD4, a “reader” protein that recognizes acetylated lysines. (See BioWorld Insight, Aug. 12, 2013.)

With the advent of JQ-1, Haldar said, “we immediately made the connection that here’s a target BRD4 that you could specifically modulate that is recognizing acetyl-lysines on chromatin.”

The team initially published work in 2013 showing that JQ-1 affected cellular processes in heart failure, and was an effective therapeutic in mice when given very early in the disease.

Patients, though, don’t show up in their doctor’s office very early in the disease. They show up with “pre-existing, often chronic heart failure,” Haldar said.

At that point, the heart has already undergone significant remodeling that includes fibrosis and an activation of innate immune pathways.

The work now published in Science Translational Medicine showed that JQ-1 had effects even when given to mice that had established heart failure either due to a heart attack, or pressure overload, but did not block exercise-induced remodeling.

The team is hoping to test JQ-1 derivatives in large animal models, and ultimately take them into the clinic. Haldar is a co-founder of Tenaya Therapeutics Inc., a company launched in December with a $50 million series A financing from The Column Group. Haldar said that while he holds a patent on BET protein inhibition in heart disease, BET proteins are only “one of many targets/pathways that Tenaya is considering.”

More:
Researchers show cancer drug class has cardiac benefits – BioWorld Online

Cancer drug class has cardiac benefits – BioWorld Online

By Anette Breindl Senior Science Editor

“With the advent of targeted cancer therapies, what we’ve found is that many of them are cardiotoxic,” Saptarsi Haldar told BioWorld Today. “Pathways that are effective in cancer are toxic in the heart.”

In the May 17, 2017, issue of Science Translational Medicine, Haldar, who is an associate investigator at the Gladstone Institute of Cardiovascular Disease, and his colleagues showed that a class of epigenetic drugs, the BET bromodomain inhibitors, may be not just an exception to that rule, but a class of drugs that has therapeutic utility in heart failure.

The team showed that the bromodomain inhibitor JQ-1 had therapeutic benefits in two separate animal models of advanced heart failure, but did not affect the beneficial changes to heart muscle cells that are a consequence of exercise.

The paper shows a potential new approach to heart failure an indication that, with a five-year survival rate of 60 percent, needs them.

It also shows a potential approach to another vexing problem, namely drugging transcription factors.

“There’s a surprisingly tractable therapeutic index for drugging transcription in diseases,” Haldar said.

While BRD4 is not itself a transcription factor, inhibiting it “dampens the transcription factor-driven network that’s driving the disease . . . This is really about dampening transcriptional rewiring,” he added.

In heart failure, those happen to be innate immune signaling and fibrotic signaling. Experiments in cardiac cells derived from induced pluripotent stem cells (iPSCs) showed that JQ-1 acted by blocking the activation of innate immune and profibrotic pathways, essentially preventing heart cells from rewiring themselves in maladaptive ways in response to being chronically overworked.

Haldar said the original idea to test whether the compound would have an effect in heart failure was based on “an educated guess.”

Previous work had shown that certain epigenetic marks, namely acetyl marks on lysines, play a role in heart failure.

“There is a lot known about lysine acetylation in heart failure,” Haldar said, and there had been previous attempts at targeting the process, which had “fallen to the wayside, in part because of issues with therapeutic index.”

Even studying the molecular details of lysine acetylation’s role in heart failure was challenging, because genetic approaches are not viable.

The problem became tractable with the synthesis of JQ-1 in the laboratory of James Bradner, who is a co-author on the Science Translational Medicine paper. The compound, which has been used to gain insight into epigenetic aspects of a large number of biological processes thanks to the decision of its developers to distribute it freely, targets BRD4, a “reader” protein that recognizes acetylated lysines. (See BioWorld Insight, Aug. 12, 2013.)

With the advent of JQ-1, Haldar said, “we immediately made the connection that here’s a target BRD4 that you could specifically modulate that is recognizing acetyl-lysines on chromatin.”

The team initially published work in 2013 showing that JQ-1 affected cellular processes in heart failure, and was an effective therapeutic in mice when given very early in the disease.

Patients, though, don’t show up in their doctor’s office very early in the disease. They show up with “pre-existing, often chronic heart failure,” Haldar said.

At that point, the heart has already undergone significant remodeling that includes fibrosis and an activation of innate immune pathways.

The work now published in Science Translational Medicine showed that JQ-1 had effects even when given to mice that had established heart failure either due to a heart attack, or pressure overload, but did not block exercise-induced remodeling.

The team is hoping to test JQ-1 derivatives in large animal models, and ultimately take them into the clinic. Haldar is a co-founder of Tenaya Therapeutics Inc., a company launched in December with a $50 million series A financing from The Column Group. Haldar said that while he holds a patent on BET protein inhibition in heart disease, BET proteins are only “one of many targets/pathways that Tenaya is considering.”

See the rest here:
Cancer drug class has cardiac benefits – BioWorld Online

Cancer-cardiac connection illuminates promising new drug for heart … – Medical Xpress

May 17, 2017 Images of heart muscle cells derived from induced pluripotent stem cells. Credit: Q. Duan et al., Science Translational Medicine (2017)

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved drugs, approximately 40% of patients with heart failure die within 5 years of their initial diagnosis.

“The current standard of care is clearly not sufficient, which highlights the urgent need for new therapeutic approaches,” said Saptarsi Haldar, MD, an associate investigator at Gladstone and senior author of a new study featured on the cover of the scientific journal Science Translational Medicine. “In our previous work, we found that a drug-like small molecule called JQ1 can prevent the development of heart failure in mouse models when administered at the very onset of the disease. However, as the majority of patients requiring treatment already have longstanding cardiac dysfunction, we needed to determine if our strategy could also treat established heart failure.”

As part of an emerging treatment strategy, drugs derived from JQ1 are currently under study in early-phase human cancer trials. These drugs act by inhibiting a protein called BRD4, a member of a family of proteins called BET bromodomains, which directly influences heart failure. With this study, the scientists found that JQ1 can effectively treat severe, pre-established heart failure in both small animal and human cell models by blocking inflammation and fibrosis (scarring of the heart tissue).

“It has long been known that inflammation and fibrosis are key conspirators in the development of heart failure, but targeting these processes with drugs has remained a significant challenge,” added Haldar, who is also a practicing cardiologist and an associate professor in the Department of Medicine at the University of California, San Francisco. “By inhibiting the function of the protein BRD4, an approach that simultaneously blocks both of these processes, we are using a new and different strategy altogether to tackle the problem.”

Currently available drugs used for heart failure work at the surface of heart cells. In contrast, Haldar’s approach goes to the root of the problem and blocks destructive processes in the cell’s command center, or nucleus.

The video will load shortly

“We treated mouse models of heart failure with JQ1, similarly to how patients would be treated in a clinic,” said Qiming Duan, MD, PhD, postdoctoral scholar in Haldar’s lab and co-first author of the study. “We showed that this approach effectively treats pre-established heart failure that occurs both after a massive heart attack or in response to persistent high blood pressure (mechanical overload), suggesting it could be used to treat a wide array of patients.”

Using Gladstone’s unique expertise, the scientists then used induced pluripotent stem cells (iPSCs), generated from adult human skin cells, to create a type of beating heart cell known as cardiomyocytes.

“After testing the drug in mice, we wanted to check whether JQ1 would have the same effect in humans,” explained co-first author Sarah McMahon, a UCSF graduate student in Haldar’s lab. “We tested the drug on human cardiomyocytes, as they are cells that not only beat, but can also trigger the processes of inflammation and fibrosis, which in turn make heart failure progressively worse. Similar to our animal studies, we found that JQ1 was also effective in human heart cells, reaffirming the clinical relevance of our results.”

The study also showed that, in contrast to several cancer drugs that have been documented to cause cardiac toxicity, BRD4 inhibitors may be a class of anti-cancer therapeutics that has protective effects in the human heart.

“Our study demonstrates a new therapeutic approach to successfully target inflammation and fibrosis, representing a major advance in the field,” concluded Haldar. “We also believe our current work has important near-term translational impact in human heart failure. Given that drugs derived from JQ1 are already being tested in cancer clinical trials, their safety and efficacy in humans are already being defined. This key information could accelerate the development of a new heart failure drug and make it available to patients more quickly.”

Explore further: Heart failure is as ‘malignant’ as some common cancers

More information: Q. Duan el al., “BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure,” Science Translational Medicine (2017). stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aah5084

A new analysis finds that, despite advances in care, men and women with a diagnosis of heart failure continue to have worse survival rates than patients with certain common cancers.

Patching a damaged heart with a patient’s own muscle stem cells improves symptoms of heart failure, according to a Phase I clinical trial reported in Journal of the American Heart Association, the Open Access Journal of the …

Researchers have completed a randomized clinical trial in patients with heart failure with preserved ejection fraction (HFpEF), which currently has no effective treatment for reducing morbidity and mortality.

A new analysis describes different classifications of patients who are hospitalized with acute heart failure based on various characteristics, which may help guide early decisions regarding triage and treatment.

(HealthDay)Patients with rheumatoid arthritis (RA) have increased risk of heart failure, according to a study published in the March 14 issue of the Journal of the American College of Cardiology.

In the largest German survey on heart failure to date, investigators found that the overall awareness of heart failure has not increased over the past decade and is not at a satisfactory level.

Shortness of breath is the No.1 complaint of people suffering from heart failure. Now a University of Guelph researcher has discovered its surprising cause – and an effective treatment – in a groundbreaking new study.

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved …

Although the absolute difference in U.S. county-level cardiovascular disease mortality rates have declined substantially over the past 35 years for both ischemic heart disease and cerebrovascular disease, large differences …

Waist-to-hip ratio may be a stronger indicator of some cardiovascular illnesses than the commonly-used measure BMI, according to a new UCL-led study.

New research has found that genetic differences in antibody genes alter individuals’ susceptibility to rheumatic heart disease, a forgotten inflammatory heart condition known as ‘RHD’ that is rife in developing countries.

People who use commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) to treat pain and inflammation could be raising their risk of having a heart attack, as early as in the first week of use and especially within …

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Go here to read the rest:
Cancer-cardiac connection illuminates promising new drug for heart … – Medical Xpress

Creative Medical Technology Holdings to Expand into 10 Billion Dollar per Year Lower Back Pain Market with … – PR Newswire (press release)

“Creative Medical Technology Holdings will develop this patent through the same process that we are using for our clinical-stage Caverstem procedure for erectile dysfunction,” stated Timothy Warbington, President and Chief Executive Officer of the Company. “We plan to identify and engage key opinion leaders who will lead clinical trials, which will serve as the basis for accelerated commercialization.”

The Company is currently running a clinical trial using autologous non-manipulated bone marrow stem cells for patients suffering from erectile dysfunction that are non-responsive to standard approaches such as Viagra.Once the trial is completed, the results will serve as the basis for marketing of disposables utilized in administration of stem cells.

“Although numerous companies are injecting stem cells directly into the disc, direct injection may only cause temporary benefit because the root cause of the pathology, in our opinion, is the reduced blood supply,” stated Dr. Amit Patel, Director of Thoracic Surgery at University of Miami and co-founder of Creative Medical Technology Holdings. “By recreating in the microenvironment of the lower back the same thing that we do in atherosclerotic heart patients, we believe we have a novel way to treat this terrible condition that wreaks havoc on our health care system.”

Several studies have shown that administration of stem cells possesses a therapeutic effect in cardiac conditions associated with poor circulation by stimulation of new blood vessel production, a process termed “angiogenesis”.The current patent covers stimulation of angiogenesis in the lower back using mesenchymal stem cells.These cells can be used from the same patient, which is considered an “autologous therapy” as well as using stem cells in a universal donor manner, which is termed “allogeneic”.

“The acquisition of this patent not only positions the company to expand into the disc degenerative space, but also provides a powerful platform for collaboration with other companies that are administering regenerative cells directly into the nucleus pulposus of the disc,” commented Thomas Ichim, Ph.D., Chief Scientific Officer of the Company and inventor of the technology. “Stem cells are like seeds, they need to be planted into fertile soil. We feel that in certain patients it is essential to treat the lumbar ischemia, which is present in some patients suffering from disc degenerative disease, which will then allow the stem cells administered directly in the disc to perform their regenerative effects.”

About US

Creative Medical Technology Holdings, Inc. is a clinical-stage biotechnology company with two focus areas; 1) personalized stem cell procedures for sexual dysfunction and infertility, and 2) universal, off-the-shelf amniotic fluid-based stem cells that possess superior healing potential without negative medical or ethical issues. Through our own research and collaborations with leading academic institutions, we have developed proprietary protocols, built an extensive intellectual property portfolio, developed complete treatment offerings for erectile dysfunction and are performing ground-breaking research with our amniotic fluid-based stem cell.

For additional information visit http://www.CREATIVEMEDICALTECHNOLOGY.com

Forward-Looking StatementsThis release may contain “forward-looking statements.” Forward-looking statements are identified by certain words or phrases such as “may”, “aim”, “will likely result”, “believe”, “expect”, “anticipate”, “estimate”, “intend”, “plan”, “contemplate”, “seek to”, “future”, “objective”, “goal”, “project”, “should”, “will pursue” and similar expressions or variations of such expressions. These forward-looking statements reflect the Company’s current expectations about its future plans and performance. These forward-looking statements rely on a number of assumptions and estimates which could be inaccurate and which are subject to risks and uncertainties. Actual results could vary materially from those anticipated or expressed in any forward-looking statement made by the Company. Please refer to the Company’s most recent Forms 10-Q and 10-K and subsequent filings with the SEC for a further discussion of these risks and uncertainties. The Company disclaims any obligation or intent to update the forward-looking statements in order to reflect events or circumstances after the date of this release.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/creative-medical-technology-holdings-to-expand-into-10-billion-dollar-per-year-lower-back-pain-market-with-acquisition-of-issued-us-stem-cell-patent-300459902.html

SOURCE Creative Medical Technology Holdings, Inc.

Home

Go here to see the original:
Creative Medical Technology Holdings to Expand into 10 Billion Dollar per Year Lower Back Pain Market with … – PR Newswire (press release)

Canadian Doctors Like Cameron Clokie Are The Innovators Behind The New Era of Regenerative Medicine – French Tribune

Heavy increases in obesity have led to an epidemic of various heart diseases, including cardiac arrests and even strokes. These dangers have compelled doctors and research specialists to seek out new ways of managing these problems. One method that has been getting a lot of attention is regenerative medicine.

This treatment method, while occasionally controversial, shows an incredible potential that could solve many serious health problems. Specialists like Dr. Cameron Clokie, a health expert with decades of experience, are currently trying to find ways to make this treatment method more accepted by those who oppose it.

The Potential for Serious Health Benefits is Huge

Regenerative medicine is the use of stem cells and other regeneration items to promote more efficient healing. Dr. Cameron Clokie has preached about the effectiveness of this treatment method for years. And it seems like the rest of the world is finally catching up with him and others like him. For example, a recent study found that stem cells could help manage cardiac and nervous system diseases.

The careful use of stem cells could regenerate damaged heart tissues and help a person avoid heart attacks and other serious problems. Even more promising, stem cells could be used to help repair nerve damage that would otherwise leave a person paralyzed for life.

Stem Cell Research Could Save Lives

Think of the stem cells in your body as building blocks that will take whatever shape is necessary. They can become heart cells and patch a hole in this vital organ. However, they could also become spinal cells and repair severe damage to this crucial part of the body.

The possibilities associated with stem cells could be potentially limitless. As they can be manipulated to take the form of any cell, they could be used to treat a variety of serious health problems. For example, they could become white blood cells and fight serious viral problems. In fact, they could even be used to treat life-threatening diseases like AIDS.

One of the understated benefits of regenerative medicine is the way that it uses actual cells from your body. Think of the problems the medical world has had with artificial hearts. While they can be beneficial to many people, they are often rejected by the fickle body as an intruder. However, creating a working heart with your body’s stem cells would eliminate that problem.

Why? Your body would recognize the heart’s cells as coming from you and would accept it more readily. As a result, you could get a new (and real) heart to replace a severely damaged one.

Profit Levels Could Also Be High

One thing that has interested many people about regenerative health and stem cell research is the potential for huge profits. Many health experts have tried to stress the ways that regenerative health could help boost the world’s economy. For example, a recent study on the financial state of this market found that it had an $18.9 billion global impact.

Even more shocking, it was projected to hit $53 billion by 2021. The major focus of this market would be in bone and joint reconstruction. The United States was expected to potentially make the largest profits in this area, which is something Dr. Cameron Clokie has emphasized in the past.

However, the European market is projected to be even bigger if the currently somewhat stagnant American regenerative market is held back by restrictive regulations or laws. In this way, well-meaning politicians could deny their constituents access to lifesaving treatments and severely impact the market at the same time.

Final Thoughts

Regenerative medicine of the type proposed by Dr. Cameron Clokie and others like him could transform the medical world. While the protests of people who find stem cells wrong are understandable, the major benefits of using them cannot be ignored.

This fact is why it is so important to help specialists like Dr. Cameron Clokie get the help they need to promote regenerative medicine breakthroughs. In this way, it is possible to solve serious health dangers.

Read the original post:
Canadian Doctors Like Cameron Clokie Are The Innovators Behind The New Era of Regenerative Medicine – French Tribune

Stem cell therapy holds promise for treating most severe cases of … – Medical Xpress

May 11, 2017

An analysis of data from the entire development program consisting of three trials assessing the feasibility of using a stem cell therapy (CD34+ cells) to treat patients with the most severe cases of angina, refractory angina (RA), showed a statistically significant improvement in exercise time as well as a reduction in mortality. Results from “CD34+ Stem Cell Therapy Improves Exercise Time and Mortality in Refractory Angina: A Patient Level Meta-Analysis” were presented today as a late-breaking clinical trial at the Society for Cardiovascular Angiography and Interventions (SCAI) 2017 Scientific Sessions in New Orleans.

One of the warning signs of coronary artery disease is angina, or chest pain, which occurs when the heart muscle does not receive enough blood. Unlike angina pectoris or “stable angina,” which can often be treated with medication, RA can be incapacitating, impacting quality of life. In the most severe cases, those with class III or IV angina, treatment options are exhausted, and patients remain severely debilitated. Unfortunately, one of the untoward consequences of the improved survival of patients with chronic ischemic heart disease is more patients with refractory angina.

A meta-analysis of three trials that each showed promising results looked at injecting RA patients with autologous CD34+ cellswhich have been shown to increase blood flowand the therapy’s effect on mortality and total exercise time (TET), an important predictor of long-term mortality.

Data from 304 patients was extracted and analyzed from phase 1 (24 patients), ACT-34 and ACT-34 extension studies (168 patients), and RENEW (112 patients), which was prematurely terminated by the sponsor due to financial considerations.

“The goal of this meta-analysis was to combine patient level data from three very similar trials to try understand what it would tell us,” said lead investigator Tom Povsic, MD, FSCAI, associate professor at the Duke Clinical Research Institute (DCRI) and an interventional cardiologist at Duke University School of Medicine.

Results showed that patients treated with CD34+ cell therapy (n=187) improved TET by 80.5 12.1, 101.8 13.7, and 90.5 14.7 seconds at three months, six months, and 12 months compared with 28.1 15.7, 48.8 18.2, and 39.5 20.3 seconds for the placebo group (n=89), resulting in treatment effects of 52.5 (p=0.002), 52.9 (p=0.009) and 50.9 (p=0.027) seconds.

The relative risk of angina was 0.90 (p=0.40), 0.81 (p=0.14), and 0.79 (p=0.17) at three months, six months, and 12 months in CD34+ treated patients.

CD34+ treatment decreased mortality by 24 months (2.6 percent vs. 11.8 percent, p=0.003). In addition, major adverse cardiac events were less frequent (29.8 percent for CD34+ patients vs. 40.0 percent for the placebo group, p=0.08).

“Therapies for these patients are direly needed,” said Povsic, “and results from our meta-analysis are very compelling. Most importantly, the number of patients in our meta-analysis approximates those who were targetedfor enrollment in RENEW, the prematurely terminated phase III study. These results suggest that had RENEW been completed, a regenerative therapy for these patients might meet criteria for approval. I still think this therapy has a lot of promise.”

Timothy Henry, MD, chief of cardiology at Cedars-Sinai Medical Center in Los Angeles, agrees “CD34+ cell therapy appears to be an extremely safe and effective therapy for this growing and challenging patient population with limited options.”

Explore further: Stem cell therapy shows potential for difficult-to-treat RA patient population

More information: Povsic presented “CD34+ Stem Cell Therapy Improves Exercise Time and Mortality in Refractory Angina: A Patient Level Meta-Analysis” on Thursday, May 11, 2017 11:30 a.m. CDT

A study using a stem cell therapy to treat challenging refractory angina (RA) patients demonstrated promising results, including improved exercise time, reduced angina and reduced mortality. The RENEW results were presented …

A two-year, multi-center clinical study with 167 patients with class III-IV refractory angina randomized to low and high dose CD34+ cells or placebo has revealed that patients who received either a high or low dose of CD34a …

The absolute cumulative probability of death at 12 months was 5 percent lower for patients who received routine invasive coronary angiography and revascularization as indicated during an unstable angina admission compared …

An injection of stem cells into the heart could offer hope to many of the 850,000 Americans whose chest pain doesn’t subside even with medicine, angioplasty or surgery, according to a study in Circulation Research: Journal …

(HealthDay)Reduced baseline levels of circulating CD34+ stem cells predict adverse cardiovascular outcomes for patients with type 2 diabetes, according to a study published online Nov. 4 in Diabetes Care.

A non-surgical treatment that uses a patient’s own bone marrow stem cells to treat chest pain or angina improved both symptoms and the length of time treated patients could be physically active, according to preliminary research …

New research has found that genetic differences in antibody genes alter individuals’ susceptibility to rheumatic heart disease, a forgotten inflammatory heart condition known as ‘RHD’ that is rife in developing countries.

People who use commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) to treat pain and inflammation could be raising their risk of having a heart attack, as early as in the first week of use and especially within …

(HealthDay)When someone goes into cardiac arrest, quick action from bystanders can have a long-lasting impact, researchers say.

Cholesterol-lowering statin drugs may have been wrongly blamed for muscle pain and weakness, said a study Wednesday that pointed the finger at a psychological phenomenon called the “nocebo” effect.

A new pilot study reports that Mexican-American stroke survivors are less likely to receive inpatient rehabilitation than non-Hispanic whites.

Less than half of individuals with peripheral artery disease, which is a narrowing of arteries to the limbs, stomach and head, are treated with appropriate medications and lifestyle counseling. These findings highlight the …

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

More here:
Stem cell therapy holds promise for treating most severe cases of … – Medical Xpress

Govt signs MoU to curb cardiac deaths in state – Times of India

Panaji: To ensure the number of emergency deaths due to cardiac-related problems are brought down, health minister Vishwajit Rane announced the signing of an MoU with ST Elevation Myocardial Infarction (STEMI) India. The organization, he said, has a protocol to handle cardiac emergency cases where such cases will be dealt with at the point of contact through the GVK 108 service.

Doctors will be trained to operate within the protocol he said, adding that it will help increase the window period after a cardiac attack and give treatment to a patient. “The whole idea is to save lives and if the window period is extended it will help saving lives of patients,” he said, adding that significant damage happens to a patient’s heart if the heart problem is not addressed.

“The problem is all casualty cases are referred to medicine and not directly to cardiology.” These, he said, should immediately be looked at by the cardiac team, he said, adding that a proposal has gone to the chief minister to add three more cardiac consultants to the cardiology wing so that 24 x7 services are made available for patients.

New fleet of 108 ambulance with trained personnel including motorcycle ambulances will be pressed into service by the end of June and first week of July, he said.

See more here:
Govt signs MoU to curb cardiac deaths in state – Times of India

Wanted: New Developer for Stem Cell Tx in Refractory Angina … – MedPage Today

NEW ORLEANS — The stem cells that have shown promise for refractory angina maintained their efficacy in a meta-analysis, as researchers once again made their case for a therapy long abandoned by its trial sponsor.

Their latest appeal: A pooling of three small, double-blind trials that randomized patients to CD34+ cell injections (n=187), placebo (n=89), and unblinded standard of care (n=28). Rates of major adverse cardiac events out to 24 months numerically favored CD34+ group (~30% versus ~40% for placebo injections, P=0.08). Deaths did reach statistical difference (~2% versus 12%, P=0.003).

Importantly, event rates were through the roof with open-label standard of care (75%), according to Thomas J. Povsic, MD, PhD, of Duke Clinical Research Institute in Durham, N.C., and colleagues at this year’s Society for Cardiovascular Angiography and Interventions meeting.

Although the placebo group improved its total exercise time, this metric was consistently around 50 seconds better in the CD34+ cohort (P

“We believe that this type of cell therapy for refractory angina is particularly promising and may improve both functional status and mortality,” according to the trialists. “It is imperative to explore methods to bring this therapy to patients.”

Lacking, however, is a funding source for clinical translation.

After going through several reorganizations, Baxter halted the RENEW trial in December 2013, reportedly for financial reasons rather than safety or efficacy problems. Povsic’s group marched on and reported last year that intramyocardial delivery of CD34+ cells was associated with fewer deaths and better exercise time.

Altogether, patients in the pooled analysis commonly had baseline diabetes (53%), hypertension (87%), hyperlipidemia (84%), and histories of percutaneous coronary intervention (88%) and coronary artery bypass graft surgery (91%).

Close to 90% were on beta blockers; over 80% on nitrates; and 50% on calcium channel blockers, Povsic added.

“It’s a shame that individual trials were stopped early. These are desperate patients that don’t have any therapy to help them. If I were to be a curmudgeon, however, I would say a 70% reduction in events — that gets attention, but that’s not realistic in an underpowered trial,” said session co-moderator Gregg W. Stone, MD, of Columbia University Medical Center/New York-Presbyterian Hospital.

“And that extra minute: how does that translate into quality of life? Is that a meaningful difference?”

Povsic argued that drugs like ranolazine (Renaxa) have been FDA-approved for just 24-45 seconds of extra exercise time — enhanced external counter pulsation therapy was green-lighted for an improvement of just 16 seconds.

The researcher said it was possible that other companies may want to pick up where Baxter left off to file for expedited FDA approval or explore the regenerative therapies initiative of the 21st Century Cures Act.

Povsic had no disclosures listed.

RENEW, ACT-34, and parts of the current meta-analysis were funded by Baxter.

2017-05-11T17:37:32-0400

See original here:
Wanted: New Developer for Stem Cell Tx in Refractory Angina … – MedPage Today

Global Human Embryonic Stem Cells Market 2017: Government Initiatives & Medical Tourism are Accelerating this … – MilTech

Summary

Orbis Research Presents Global Human Embryonic Stem Cells Market Research Report which Examine into the present trends, highlights the recent market growth, sales volume, Demand Scenarios and Opportunities emerging for business players in the near future.

Description

The Global Human Embryonic Stem Cells Market is estimated to be USD XX billion in 2017 and is expected to reach USD XX billion by 2022, registering a healthy CAGR of XX%, during 2017-2022 (forecast period).

The increase in malignant, cardiac, & neurological disorders, immediate need for effective and novel therapies, the rising human embryonic stem cell awareness and better healthcare infrastructure with government initiatives are expected to accelerate the global human embryonic stem cells market, during the forecast period.

The major companies discussed in this report are

A majority of companies are investing in the human embryonic stem cell research, globally. The high-prevalence of cardiac and malignant diseases, increasing R&D investments & research initiatives, increasing support from government & private institutions and rapid growth in medical tourism are accelerating the market growth. However, the stringent regulatory guidelines and ethical & moral concerns are restraining the market.

Get a PDF Sample of Global Human Embryonic Stem Cells Market Report at: http://www.orbisresearch.com/contacts/request-sample/280434

The global embryonic stem cells market is segmented based on application and geography. The applications segment includes regenerative medicine, stem cell biology research, tissue engineering and toxicology testing. Based on geography, the market is segmented into North America, Europe, Asia-Pacific, the Middle East & Africa and Latin America. The Asia-Pacific human embryonic stem cells market has the potential, owing to increasing initiatives of the governments & private organizations for research in human embryonic stem cells.

Key Deliverables

Market analysis, with region-specific assessments and competition analysis on a global and regional scale.

Market definition along with the identification of key drivers and restraints.

Identification of factors instrumental in changing the market scenario, growing prospective opportunities, and identification of key companies that can influence the market.

Extensively researched competitive landscape section with profiles of major companies, along with their market share.

Identification and analysis of the macro and micro factors that affect the market on both, global and regional scale.

A comprehensive list of key market players along with the analysis of their current strategic interests and key financial information.

A wide-range of knowledge and insights about the major players in the industry and the key strategies adopted by them to sustain and grow in the studied market

Insights on the major countries/regions where the industry is growing, and identify the regions that are still untapped.

See more here:
Global Human Embryonic Stem Cells Market 2017: Government Initiatives & Medical Tourism are Accelerating this … – MilTech

Tucson Tech: University of Arizona startup advances living heart patch – Arizona Daily Star

Repairing beating human hearts with living patches is the aim of Avery Therapeutics, a startup company founded on technology developed by University of Arizona researchers.

The company recently licensed a new heart-graft technology from the UA and is working to get it into human clinical trials to treat heart failure within a few years.

Avery was co-founded in 2014 by cardiologist Dr. Steve Goldman of the UAs Sarver Heart Center and Jordan Lancaster, who earned his UA doctorate in physiology while working in Goldmans lab.

Averys biologically active heart graft, dubbed MyCardia, combines commercially available living cells called fibroblasts, heart-muscle cells derived from stem cells and a biologically absorbable scaffold.

The resulting graft can be sewn onto a live heart where it can build up new muscle cells to improve heart function as it grows with the patients own tissue.

You can basically think of it as a living Band-Aid, said Lancaster, who is chief science officer of Avery.

Goldman and Lancaster began research in the area in 2009 at the Southern Arizona VA Health Care System, where Goldman was chief of cardiology, for a San Francisco-based company developing a heart graft using fibroblasts on a scaffold material to treat angina, or heart-related chest pain.

That project ended when studies showed little improvement with the graft, Lancaster said.

But Goldman and Lancaster extended the research at the UA, tapping Nobel Prize-winning technology developed by Japanese scientists using so-called induced pluripotent stem cells which have the ability to turn into any kind of cell to create a new kind of living heart patch.

The Avery research team already has published scientific studies showing improvement in heart function in rats treated with the heart patch.

Immersed in a nutritive medium, the companys prototype patches contract in rhythm, on their own.

Theyre waving or winking at you, every time you see them in the lab, Lancaster said.

Though much work remains to be done even to get to human clinical trials, Avery is proceeding apace to commercialize the technology with the help of Tech Launch Arizona, the UAs technology-commercialization arm.

Jen Koevary, who earned her doctorate in biomedical engineering from the UA, joined Avery as chief operating officer after helping the company as a business-development officer for TLA.

Avery also is being advised by Bruce Burgess, a TLA mentor-in-residence with more than 30 years of entrepreneurial experience in medical devices, diagnostics and drug delivery.

Though an approved product is still years away, the company has published numerous scientific papers, raised hundreds of thousands of dollars in research grants and won one patent, with more in the pipeline.

In August, Avery was awarded a Phase 1 Small Business Innovation Research grant of nearly $500,000 by the National Institutes of Healths National Heart, Lung and Blood Institute to develop manufacturing, cryopreservation, storage and reconstitution methods for the MyCardia patch.

Lancaster noted that Phase I SBIR contracts are generally up to $150,000, so the much larger NIH grant was significant.

The company also has won a $750,000 grant through the UA from the Arizona Biomedical Research Commission, and $60,000 in cash and prizes at Tucsons Get Started business-pitch competition in October.

The company has delivered its pitch internationally, at the Falling Walls Venture conference in Berlin in November.

Last week, Avery presented at the TechCode event space in Mountain View, California, where Silicon Valley investors learned about the company along with four other UA spinoffs.

Koevary said the company will keep pitching its technology and writing grants to raise money for further studies, likely including a bid for a larger Phase II SBIR grant.

Avery plans to present its technology at the 2017 BIO International Convention one of the biggest biotech events in the world in San Diego in June.

Scientifically, the next step is to test the patch in large-animal studies using pigs, which provide a close match to humans, she said.

Theres a lot that still needs to be done, Koevary said, noting that induced pluripotent stem cells have been tested in just one clinical trial, a Japanese effort focused on treating the eye.

We have to do a lot of work on the manufacturing side, in proving we can manufacture a quality product every time, she said.

After the animal studies the company also will have to submit a rigorous lab-practices study, which the company hopes will pave the way to start human clinical trials by 2020, Koevary said.

Koevary said the company will likely need upward of $10 million to take the heart patch to human clinical trials.

Avery is working on a private investment round among friends and family, she said, adding that the company also is establishing relationships with investor groups and looking at partnerships with established biomedical companies.

Researchers worldwide are working on regenerative tissue therapies, including a University of Minnesota group that recently published a paper on a heart graft made by 3-D printing heart-muscle stem cells and growing them in the lab.

But Lancaster said Avery named for his daughters middle name has a big advantage with Goldman and his lab, which he said offers a rare combination of clinical expertise in cell culturing, bioengineering and animal modeling.

Being able to cover that spectrum has really allowed us to move faster than others, Lancaster said. I think weve got a very good head start on a lot of people.

Tucson Tech runs Thursdays or Sundays in the Star. Contact senior reporter David Wichner at dwichner@tucson.com or 573-4181. On Twitter: @dwichner

More here:
Tucson Tech: University of Arizona startup advances living heart patch – Arizona Daily Star

Will Stem Cell Research Change Treatment of Heart Disease? – Health Essentials from Cleveland Clinic (blog)

Q: Ive been reading a lot about stem cells recently. Willstem cell research change the treatment of heart disease?

A: Theres some exciting early data where scientists have been able to use stem cells for regeneration of cardiac tissue, in particular certain parts of the heart or maybe even an entire heart in mice or rats.

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

However, its not been done yet in humans reliably and that would be the next step. If the research bears out, we may see this as an option for heart patients in perhaps five to 10 years.

The area where stem cells might first be used is in patients who have had damage to their heart because of a heart attack. These patients have scarring on the heart and that area of the heart is not beating anymore. If we can regenerate cardiac tissue to replace this scarred tissue, the hope is to get the heart fully working again.

Growing whole new hearts will likely be later down the line and will depend on the success of the research.

Preventive cardiologistHaitham Ahmed, MD, MPH

See original here:
Will Stem Cell Research Change Treatment of Heart Disease? – Health Essentials from Cleveland Clinic (blog)

Kidney research leads to surprising discovery about how the heart forms – Science Daily

Kidney research at the University of Virginia School of Medicine has unexpectedly led to a discovery about the formation of the heart, including the identification of a gene responsible for a deadly cardiac condition.

UVA scientists were surprised to discover that the heart’s inner lining forms from the same stem cells, known as “precursor cells,” that turn into blood. That means a single type of stem cell turns into both our blood and a portion of the organ that will pump it.

The researchers determined that a particular gene, S1P1, is vital for the proper formation of the heart. Without it, the heart tissue produced by the precursor cells develops a sponginess that compromises the heart’s ability to contract tightly and pump blood efficiently. In people, that is known as ventricular non-compaction cardiomyopathy, a dangerous condition that often leads to early death.

“Many patients who suffer from untreatable chronic diseases, including heart and kidney diseases, are in waiting lists for limited organ transplantation. Therefore, there is an urgent need to understand what happens to the cells during disease and how can they be repaired,” said researcher Yan Hu, PhD. “Every organ is a complex machine built by many different cell types. Knowing the origin of each cell and which genes control their normal function are the foundations for scientists to decipher the disease process and eventually to find out how to guide the cells to self-repair or even to build up a brand new organ using amended cells from the patients.”

Far-Reaching Consequences

The researchers, led by Maria Luisa S. Sequeira-Lopez, MD, of UVA’s Child Health Research Center, were investigating how the kidney forms when they noted that the deletion of the S1P1 gene in research mice had deadly consequences elsewhere in the body. “We were studying the role of these genes in the development of the vasculature of the kidney,” she recalled. “The heart is the first organ that develops, and so when we deleted this gene in these precursor cells, we found that it resulted in abnormalities of the heart, severe edema, hemorrhage and low heart rate.”

That led them to look more closely at the heart. It was then that they discovered the gene deletion had caused thin heart walls and other cardiac problems in developing mice embryos. “So then we had to study the heart when the kidneys were still not even formed,” she said. “We had to go far outside our comfort zone.”

Their findings would prove unexpected even for scientists who specialize in the development of the heart. “For a long time, scientists believed that each organ developed independently of other organs, and the heart developed from certain stem cells and blood developed from blood stem cells,” explained researcher Brian C. Belyea, MD, of the UVA Children’s Hospital. “A number of studies done in this lab and others, including this work, shows that there’s much more plasticity in these precursor cells. What we found is that cardiac precursor cells that are present in the embryonic heart do indeed give rise to components of the heart in adults but also give rise to the blood cells.”

The researchers were so surprised by their discovery that they went back and validated their findings repeatedly, using multiple techniques, including new techniques that they developed.

Belyea said that the discovery about the important role of the S1P1 gene may one day lead to better treatments for that condition. “We hope,” he said, “that this is a stepping stone for our clinical colleagues.”

Story Source:

Materials provided by University of Virginia Health System. Note: Content may be edited for style and length.

See the original post:
Kidney research leads to surprising discovery about how the heart forms – Science Daily

Fixing broken hearts through tissue engineering – Science Daily

The third annual Cardiovascular Tissue Engineering Symposium met at the University of Alabama at Birmingham last month, a gathering of noted physicians and scientists who share the goal of creating new tissues and new knowledge that can prevent or repair heart disease and heart attacks.

Talks ranged from the cutting-edge translational work of Phillippe Menasche, M.D., Ph.D., professor of thoracic and cardiovascular surgery, Paris Descartes University, to the basic biology research of Sean Wu, M.D., Ph.D., an associate professor of medicine, Stanford University School of Medicine. Menasche’s work pioneers human treatment with engineered heart tissue. Wu’s work opens the door to generating heart chamber-specific cardiomyocytes from human induced pluripotent stem cells, which act similarly to embryonic stem cells, having the potential to differentiate into any type of cell.

Menasche has placed engineered heart tissue derived from embryonic stem cell-derived cardiac cells onto the hearts of six heart attack patients in France in an initial safety study for this engineered tissue approach. Wu has used single-cell RNA sequencing to show 18 categories of cardiomyocytes in the heart, differing by cell type and anatomical location, even though they all derived from the same lineage.

“We are creating a new community of engineer-scientists,” said Jay Zhang, M.D., Ph.D., chair and professor of the UAB Department of Biomedical Engineering. In their welcoming remarks, both Selwyn Vickers, M.D., dean of the UAB School of Medicine, and Victor Dzau, M.D., professor of medicine at Duke University School of Medicine and president of the National Academy of Medicine, spoke of the growing convergence between scientists and physicians that is leading to tremendous possibilities to improve patient care.

The tissue engineering field is moving fast.

Cardiac progenitor cells that can contribute to growth or repair injury in the heart were only discovered in 2003, says symposium presenter Michael Davis, Ph.D., associate professor of Medicine, Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory University School of Medicine. In 2006, the Japanese scientist Shinya Yamanaka first showed how to transform adult cells into induced pluripotent stem cells. This potentially provides feedstock for tissue engineering using either pluripotent cells or specific progenitor cells for certain tissue lineages.

One example of the pace of change was given by Bjorn Knollman, M.D., Ph.D., professor of medicine and pharmacology at Vanderbilt University School of Medicine. Knollman noted an “ugly truth” that everyone recognized in 2013 — that cardiomyocytes derived from induced pluripotent stem cells were nothing like normal adult cardiomyocytes in shape, size and function.

He described the improved steps like culturing the derived cardiomyocytes in a Matrigel mattress and giving them a 14-day hormone treatment that have led to derived cardiomyocytes with greatly improved cell volume, morphology and function. His take-home message: In just four years, from 2013 to 2017, researchers were able to remove the differences between induced pluripotent stem cell-derived cardiomyocytes and normal adult cardiomyocytes.

In other highlights of the symposium, Joo Soares, Ph.D., a research scientist for the Center for Cardiovascular Simulation, University of Texas at Austin, explained how subjecting engineered heart valve tissue to cyclic flexure as it is grown in a bioreactor leads to improved quantity, quality and distribution of collagen, as opposed to tissue that is not mechanically stressed.

Sumanth Prabhu, M.D., professor and chair of the Division of Cardiovascular Disease, UAB School of Medicine, talked about the role of immune cells in cardiac remodeling and heart failure. He noted the distinct phases after a heart attack — acute inflammation and dead tissue degradation, zero to four days; the healing phase of resolution and repair, four to 14 days; and the chronic ischemic heart failure that can occur weeks to months later. Prabhu described experiments to show how specialized spleen macrophages — specifically marginal-zone metallophilic macrophages — migrate to the heart after a heart attack and are required for heart repair to commence.

Nenad Bursac, Ph.D., professor of Biomedical Engineering, Duke University School of Medicine, described his advances in engineering vascularized heart tissue for repair after a heart attack. Bursac said a better understanding of how to grow the tissue from heart tissue progenitor cells has allowed formation of mature “giga” patches up to 4 centimeters square that have good propagation of heartbeat contractions and spontaneous formation of capillaries from derived-vascular endothelial and smooth muscle cells. These patches are being tested in pigs.

Duke University’s Victor Dzau gave a perspective of the paracrine hypothesis over the past 15 years. In 2003, researchers had seen that applying mesenchymal stem cells to a heart attack area led to improved heart function, with beneficial effects seen as early as 72 hours. However, there was little engraftment and survival of the stem cells. Thus was born the hypothesis, which has been worked out in detail since then — that stem cells do their work by release of biologically active factors that act on other cells, similar to the way that paracrine hormones have their effect only in the vicinity of the gland secreting it.

Joseph Wu, M.D., Ph.D., professor of radiology, Stanford University School of Medicine, showed how heart cells derived from induced pluripotent stem cells could be used to develop personalized medicine approaches for cancer patients. The problem, he explained, is that some cancer patients are susceptible to a deadly cardiotoxicity when treated with the potent drug doxorubicin. Hence, the drug has a black box warning, the strictest warning mandated by the Food and Drug Administration. Wu was able to use a library of induced pluripotent stem cell-derived cardiomyocytes to associate certain genotypes and phenotypes with doxorubicin sensitivity, in what he called a “clinical trial in a dish.” From this knowledge, it will be possible to look at the transcriptome profile in patient-specific cardiomyocytes derived from induced pluripotent stem cells to predict patient-specific drug safety and efficacy, thus fulfilling the definition of precision medicine — the right treatment at the right time to the right person.

In all, UAB’s Cardiovascular Tissue Engineering Symposium included more than 30 presentations. The entire symposium will be summarized in a paper for the journal Circulation Research, expected to be published shortly, Zhang says.

Presentations of the 2015 Cardiovascular Tissue Engineering Symposium were published in the journal Science Translational Medicine, and the presentations of the 2016 Cardiovascular Tissue Engineering Symposium were published in the journal Circulation Research.

Read the original post:
Fixing broken hearts through tissue engineering – Science Daily

Kidney research leads to heart discovery – Newsplex – The Charlottesville Newsplex

CHARLOTTESVILLE, Va. (NEWSPLEX) — Researchers at the University of Virginia School of Medicine were looking into kidneys and learned more about the formation of the heart.

They also identified a gene that is responsible for a deadly cardiac condition.

According to a release, scientists discovered the heart’s inner lining forms from the same stem cells, known as precursor cells, that turn into blood.

That means a single type of stem cell created both the blood and part of the organ that pumps it.

A particular gene, called S1P1, is necessary for the proper formation of the heart, and without it, the tissue develops a sponginess that compromises the heart’s ability to contract tightly and pump blood efficiently.

That condition is called ventricular non-compaction cardiomyopathy, which often leads to early death.

“Many patients who suffer from untreatable chronic disease, including heart and kidney disease, are in waiting lists for limited organ transplantation. Therefore, there is an urgent need to understand what happens to the cells during disease and how can they be repaired,” said researchers Yan Hu, PhD. “Every organ is a complex machine built by many different cell types. Knowing the origin of each cell and which genes control their normal function are the foundations for scientists to decipher the disease process and eventually to find out how to guide the cells to self-repair or even to build up a brand new organ using amended cells from the patients.”

The researchers were looking into how the kidneys form when they noted a deletion of the S1P1 gene in research mice led to deadly consequences elsewhere in the bodies of the mice.

“We were studying the role of these genes in the development of the vasculature of the kidney,” said Maris Luisa S. Sequeira-Lopez, MD, of UVA’s Child Health Research Center. “The heart is the first organ that develops, and so when we deleted this gene in these precursor cells, we found that it resulted in abnormalities of the heart, severe edema, hemorrhage and low heart rate.”

In looking closer at the heart, the researchers discovered the gene deletion caused thin heart walls and other cardiac problems in developing mice embryos.

“For a long time, scientists believed that each organ developed independently of other organs, and the heart developed from certain stem cells and blood developed from blood stem cells,” said researcher Brian C. Belyea, MD, of the UVA Children’s Hospital. “A number of studies done in this lab and others, including this work, shows that there’s much more plasticity in these precursor cells. What we found is that cardiac precursor cells that are present in the embryonic heart do indeed give rise to components of the heart in adults but also give rise to the blood cells.”

He also said the discovery may one day lead to the development of better treatments for the cardiac condition.

The findings have been published in the journal Scientific Reports.

Link:
Kidney research leads to heart discovery – Newsplex – The Charlottesville Newsplex

Archives