Archive for the ‘Cardiac Stem Cells’ Category

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In the U.S., someone suffers a heart attack every 34 secondstheir heart is starved of oxygen and suffers irreparable damage. Engineering new heart tissue in the laboratory that could eventually be implanted into patients could help, and scientists are reporting a promising approach tested with rat cells. They published their results on growing cardiac muscle using a scaffold containing carbon nanofibers in the ACS journal Biomacromolecules.

Gordana Vunjak-Novakovic, Rui L. Reis, Ana Martins and colleagues point out that when damaged, adult heart tissue can't heal itself very well. The only way to fix an injured heart is with a transplant. But within the past decade, interest in regenerating just the lost tissue has surged. The trick is to find materials that, among other things, are nontoxic, won't get attacked by the body's immune system and allow for muscle cells to pass the electrical signals necessary for the heart to beat. Previous research has found that chitosan, which is obtained from shrimp and other crustacean shells, nearly fits the bill. In lab tests, scientists have used it as a scaffold for growing heart cells. But it doesn't transmit electrical signals well. Vunjak-Novakovic's team decided to build on the chitosan development and coax it to function more like a real heart.

To the chitosan, they added carbon nanofibers, which can conduct electricity, and grew neonatal rat heart cells on the resulting scaffold. After two weeks, cells had filled all the pores and showed far better metabolic and electrical activity than with a chitosan scaffold alone. The cells on the chitosan/carbon scaffold also expressed cardiac genes at higher levels.

Explore further: Researchers develop spring-like fibers to help repair damaged heart tissue

More information: "Electrically Conductive Chitosan/Carbon Scaffolds for Cardiac Tissue Engineering" Biomacromolecules, Just Accepted Manuscript. DOI: 10.1021/bm401679q

Abstract In this work carbon nanofibers were used as doping material to develop a highly conductive chitosan-based composite material. Scaffolds based on chitosan only and chitosan/carbon composites were prepared by precipitation. Carbon nanofibers were homogeneously dispersed throughout the chitosan matrix, and the composite scaffold was highly porous with fully interconnected pores. Chitosan/carbon scaffolds had elastic modulus of 28.1 3.3 KPa, similar to that measured for rat myocardium, and excellent electrical properties, with conductivity of 0.25 0.09 S/m. The scaffolds were seeded with neonatal rat heart cells and cultured for up to 14 days, without electrical stimulation. After 14 days of culture, the scaffold pores throughout the construct volume were filled with cells. The metabolic activity of cells in chitosan/carbon constructs was significantly higher as compared to cells in chitosan scaffolds. The incorporation of carbon nanofibers also led to increased expression of cardiac-specific genes involved in muscle contraction and electrical coupling. This study demonstrates that the incorporation of carbon nanofibers into porous chitosan scaffolds improved the properties of cardiac tissue constructs, presumably through enhanced transmission of electrical signals between the cells.

The threat from a heart attack doesn't end with the event itself. Blockage of blood flow to the heart can cause irreversible cell death and scarring. With transplants scarce, half the people who live through a heart attack ...

(Medical Xpress) -- Researchers at Columbia Engineering have established a new method to patch a damaged heart using a tissue-engineering platform that enables heart tissue to repair itself. This breakthrough, ...

For the first time, a mouse heart was able to contract and beat again after its own cells were stripped and replaced with human heart precursor cells, said scientists from the University of Pittsburgh School of Medicine. ...

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Toward fixing damaged hearts through tissue engineering

TAMPA, Fla. (PRWEB) January 22, 2014

Societys continual, obsessive search for perpetual youth has lead many on a tumultuous path of medical mayhem from shots to creams and a variety of procedures in between.

A leader in modern medicine, Dr. Burton Feinerman has always been at the forefront of new and life changing procedures in the healthcare community. Feinerman's experience includes his time as a key research associate at the Papanicolau Cancer Research Institute in Miami.

His career took a glamorous turn when he became a concierge physician to the stars at his office in Maui, Hawaii. He has treated a variety of high-profile clientele including celebrities Eddie Murphy, Larry David, Pink, Brittney Spears, Nick Nolte, Christian Slater, Arnold Schwarzenegger and Oprah, who once thanked him with an autographed magazine for the shot in the tush.

Staying true to his mission to find relief for those afflicted with incurable diseases, Feinerman soon focused his efforts on the innovative and unfamiliar world of cell regeneration and gene therapy. As one of the original physician scientists to create stem cell protocols for incurable diseases, Feinerman now runs his clinic in Tampa, Fla. where he treats patients with conditions such as Alzheimers, ALS, Autism, brain damage, Cerebral Palsy, Multiple Sclerosis, Spinal Cord Injury, Parkinsonism, Heart Disease, COPD, diabetes, Chronic Kidney Disease, Pulmonary Fibrosis, Tay Sachs, Sandhoff Disease, Stargardt Disease, Huntington Disease, Scleroderma, Lupus, Rheumatoid Arthritis, Crohns Disease, cancer of all types, Macular Degeneration and Retinitis Pigmentosa.

The emerging developments in stem cell therapy, gene therapy, nanotechnology and tissue engineering offer new hope to millions of patients, said Feinerman.

Stem Cells and Sex Wars By: Dr. Burton Feinerman ISBN: 978-1481774789 Available at Amazon, Barnes and Noble and Authorhouse online bookstores.

About the authors A graduate of New York Medical College, Dr. Burton Feinerman also received extensive postgraduate training from Long Island College Hospital and the Mayo Clinic. He served as chief medicine for the U.S. Army, as part of the 98th General Hospital in Germany as well as chairman of medicine at Miami General Hospital, Opa-Locka Hospital, N. Miami General Hospital and chairman of cancer technologies Kids Medical Centers of America. Active in many industry organizations, Feinerman is a member of the Society of Apheresis, the Society of Bone Marrow Blood Transplantation, the International Society for Cellular Therapy, the Society for Cranial Transplantation and Brain Repair, and the Society for Cardiac Translational Therapy. With over 55 years of experience in medical practice, he is currently the president and CEO of Stem Cell Regen Med.

Continued here:
Dr. Burton Feinerman Shares Experiences from Celebrity Care to Modern Medicine

Scientists at the University of Illinois have created a minuscule swimming machine, just under eight-one-hundredth of an inch (1.95 mm), thats powered by beating heart muscle cells. Details of their invention, which might someday have medical applications for precision-targeting medication and micro-surgery inside the body, was published in the January 17, 2014 issue of the journal Nature Communications.

Professor Taher Saif, of the University of Illinois, leads the team that created what they call a tiny bio-hybrid machine or bio-bot. He said, in a press release:

Micro-organisms have a whole world that we only glimpse through the microscope. This is the first time that an engineered system has reached this underworld.

The bio-bot has a flagella-shaped body, that is, a cell with a long tail, like a sperm cell. The machine body is made from a flexible polymer thats coated with a substance called fibronectin, which provides an attachment surface for cardiac cells cultured on the bots head and tail. In a yet-to-be understood phenomenon, the heart cells communicate, align with each other, and synchronize their contraction-relaxation beat to move the machines tail. This motion creates waves in the fluid that propels the bot forward.

The scientists also created a faster-swimming bio-bot model with two tails. They think that a bio-bot with several tails could even be used to steer towards specific locations. This could give rise to tiny machine deployed to work on a microscopic scale. Saif commented:

The long-term vision is simple. Could we make elementary structures and seed them with stem cells that would differentiate into smart structures to deliver drugs, perform minimally invasive surgery or target cancer?

Bottom-line: University of Illinois scientists have created a microscopic swimming bio-bot thats powered by beating cardiac muscle cells. The tiny machine, measuring just under eight-one-hundredth of an inch (1.95 mm), may someday be adapted for medical applications inside the body. The journal Nature Communications published details of this research on January 17, 2014.

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Tiny machines that swim using heart muscle cells

The Mayo Clinic in Rochester announced Friday that a decade-long research project on using stem cells to repair damaged heart tissue has won federal approval for human testing, a step that could have implications for millions of Americans with heart disease.

The U.S. Food and Drug Administration has approved a multistate clinical trial of 240 patients with chronic advanced symptomatic heart failure to determine if the procedure produces a significant improvement in heart function.

Safety testing in humans, completed earlier in Europe, showed a preliminary 25 percent improvement in cardiac outflow, according to Dr. Andre Terzic, director of the Mayo Clinic's Center for Regenerative Medicine.

The procedure could be a "paradigm shift" in the treatment of heart disease, Terzic said.

Treatments going forward won't just focus on easing the symptoms of the disease, Terzic said, but rather, on curing it.

The process, developed in collaborations with Cardio3 BioSciences of Belgium, involves harvesting stem cells from a heart patient's bone marrow in the hip, directing the cells to become "cardiopoietic" repair cells, then injecting them back into the heart to do their work.

Mayo researcher Dr. Atta Behfar and other members of Terzic's team isolated hundreds of proteins involved in the transcription process that takes place when stem cells are converted to heart cells. They identified eight proteins that were crucial in the development of heart cells and used them to convert stem cells into heart cells.

"This is unique in the world," Terzic said.

Forty hospitals in Europe and Israel are enrolling heart patients in human trials to test Mayo's new treatment regimen for heart failure. Enrollments are expected to be completed by the end of the year, and early results should be available in 2015, according to Dr. Christian Homsy, CEO of Cardio3 BioSciences.

If things go well, patients could start being treated with the new technology by the end of 2016 in Europe, and perhaps a year later in the United States.

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Mayo wins FDA approval to test stem-cell technique for heart patients

Welcome to this week's Biotech Stock Mailbag. Before I kick off, a few housekeeping items to note:

I launched a new blog on TheStreet this week. It's called Adam's Biotech Beat. I know, not the most original name but straightforward. I'll have more to say about the blog later, but please bookmark the page and check it often. You'll see me posting a lot of intraday news and analysis, plus it's a great way to keep track of all my tweets.

The J.P. Morgan Healthcare Conference starts Monday in San Francisco. I'm flying out there Sunday and will be providing live coverage from the presentations and breakout rooms.

Chelsea Therapeutics (CHTP) and its hypotension drug Northera will be the star of an FDA advisory panel on Tuesday. I have invited healthcare investor and TheStreet contributing writer Aafia Chaudhry to live-blog the Chelsea panel, so please tune into that.

Read this article:
Biotech Stock Mailbag: NeoStem, MannKind, Inovio

Monday, October 11, 2010 - Noon

Stephen Ellis, MD Section Head of Invasive/Interventional Cardiology, Robert and Suzanne Tomsich Department of Cardiovascular Medicine

Stem cells are natures own transformers. When the body is injured, stem cells travel to the scene of the accident and help heal damaged tissue. The cells do this by transforming into whatever type of cell has been injured- bone, skin and even heart tissue. Researchers at Cleveland Clinic believe that the efficiency of stem cells for treating heart tissue can be boosted and help the body recover faster and better from heart attacks. Join us in a free online chat with cardiologist Stephen Ellis, MD. Dr. Ellis is leading one of the clinical trials and will be answering your questions about stem cell therapy for heart disease.

Cleveland_Clinic_Host: Welcome to our "Stem Cell Therapy for Heart Disease" online health chat with Stephen Ellis, MD. Dr. Ellis is leading one of the research studies for stem cell therapy and heart disease so he will be answering a variety of questions on the topic. We are very excited to have him here today!

Thank for joining us Dr. Ellis, let's begin with the questions.

Dr__Ellis: Thank you for having me today.

Robert_B: I have a question on Stem Cell and stabilizing a two chamber heart condition.. Could donor adult stem cells help stabilize the heart and repair some of the damage? Patient also suffers from cardiac sclerosis of the liver.

Dr__Ellis: Stem cells are currently being evaluated to see if they may or may not strengthen hearts previously damaged by heart attacks or other conditions. They are considered experimental for this purpose. There are several ongoing clinical trials available in the U.S.

cabbagepatch: I have been going through other tests for heart transplant consideration, & with everything I have been going through would I be a candidate for heart stem cell repair? How would I find out? My cardiologist is Dr. Hsich in Cleveland.

Dr__Ellis: You may be a candidate for the NIH FOCUS trial at the Cleveland Clinic. Please ask Dr. Hsich - she would be able to help you.

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Stem Cell Therapy for Heart Disease Webchat - Dr. Ellis

Keeping in tradition with the Us commitment to advance the fields of medicine and surgery, our physicians are focusing on regenerative medicine as the next frontier in treating cardiovascular disease. Researchers within the Cardiovascular Center estimate cell therapy will be FDA-approved within three years. The goal of this therapy is to give cells back to the heart in order for it to grow stronger, work harder, and function more like a younger heart. Currently, studies include the potentiality of injecting cardiac repair cells into patients hearts to improve function.

This is the first trial of its kind in the United States, providing heart patients who have limited or no other options with a viable treatment. Using some of the best imaging technology, researchers have been able to see improvements in patients within six months after injecting their own cells directly into the left ventricle of the heart during minimally invasive surgery.

To contact us, please use the contact number provided.

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Heart Stem Cell Therapy - - - University of Utah Health Care ...

PUBLIC RELEASE DATE:

23-Dec-2013

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Dec. 23, 2013) Cell-based therapies have been shown to enhance cardiac regeneration, but autologous (patient self-donated) cells have produced only "modest results." In an effort to improve myocardial regeneration through cell transplantation, a research team from Germany has taken epithelial cells from placenta (amniotic epithelial cells, or AECs) and converted them into mesenchymal cells. After transplanting the transitioned cells into mice modelling a myocardial infarction, the researchers found that the epithelial-to-mesenchymal transition (EMT) was beneficial to cardiac regeneration by lowering infarct size. They concluded that EMT enhanced the cardioprotective effects of human AECs.

The study will be published in a future issue of Cell Transplantation but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1046Roy.

The authors noted that AECs have been shown to share characteristics of pluripotent cells that are able to transform into all other kinds of cells, and that their isolation and clinical-grade expansion of AECs is "relatively straightforward."

"Our hypothesis was that EMT would improve cardiac regeneration capacity of amniotic epithelial cells by increasing their mobility and extracellular matrix modulating capacity," said study corresponding author Dr. Christof Stamm of the Berlin Brandenburg Center for Regenerative Therapies, Berlin, Germany. "Indeed, four weeks after the mice were modeled with myocardial infarction the mice subsequently treated with EMT-AECs were associated with markedly reduced infarct size."

According to the researchers, as a result of the EMT process the AECs lost their "cobblestone" structure and acquired a fibroblastoid shape which was associated with a number of biological alterations that ultimately aided their mobility and altered their secretions.

One direct result of the EMT-AEC treatment was that EMT-AEC-treated hearts displayed "better global systolic function and improved longitudinal strain rate in the area of interest."

The researchers added that while AECs may be useful in the context of cardiovascular regeneration, it is unclear whether the usefulness requires "actual stemness" or "pluripotency-unrelated secretory mechanisms."

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Transitioning epithelial cells to mesenchymal cells enhances cardiac protectivity

Florida Hospital Pepin Heart Institute is First in West & Central Florida to Perform a Groundbreaking Stem Cell Clinical Trial for Heart Failure Patients

The first patient has been treated as part of The ATHENA Trial, which derives stem cells from the patientsown adipose (fat) tissue and injects extracted cells into damaged parts of the heart.

TAMPA, Florida (December 20, 2013) Florida Hospital Pepin Heart Institute and Dr. Kiran C. Patel Research Institute announced the first patient, a 59 year old Clearwater man, has been treated as part of the ATHENA clinical trial. The trial, sponsored by San Diego-based Cytori Therapeutics, derives stem cells from the patients own fat tissue and injects extracted cells into damaged parts of the heart. The ATHENA trial is a treatment for chronic heart failure due to coronary heart disease. Dr. Charles Lambert, Medical Director of Florida Hospital Pepin Heart Institute, is leading the way for the first U.S. FDA approved clinical trial using adipose-derived regenerative cells, known as ADRCs, in chronic heart failure patients. I am pleased to report that all procedures went well. The patient is doing well, he was released and is recovering at home. We look forward to following his progress over the coming months, said Dr. Charles Lambert. Heart failure (HF) can occur when the muscles of the heart become weakened and cannot pump blood sufficiently throughout the body. The injury is most often caused by inadequate blood flow to the heart resulting from chronic or acute cardiovascular disease, including heart attacks. The ATHENA clinical trial procedure is a three step process. First, the trial involves the collection of fat from the patients body by liposuction. Then the fat sample is filtered through a machine that extracts out the stem cells. Finally, the stem cells are injected into the damaged part of the patients heart. During this first case at Florida Hospital Pepin Heart Institute, Dr. Paul Smith performed the liposuction to obtain the fat sample, a team at the Dr. Kiran C. Patel Research Institute isolated stem cells from the fat sample and then Dr. Charles Lambert performed the cell therapy by direct injection into the patients heart. Pepin Heart and Dr. Kiran C. Patel Research Institute is exploring and conducting leading-edge research to develop break-through treatments long before they are even available in other facilities. Stem cells have the unique ability to develop into many different cell types, and in many tissues serve as an internal repair system, dividing essentially without limit to replenish other cells, said Dr. Lambert.

The Pepin Heart Institute has a history of cardiovascular stem cell research as part of the NIH sponsored Cardiac Cell Therapy Research Network (CCTRN) as well as other active cell therapy trials. The trial is a double blind, randomized, placebo controlled study designed to study the use of a patients own Adipose-Derived Regenerative Cells (ADRCs) to treat chronic heart failure from coronary heart disease in patients who are on maximal therapy and still have heart failure symptoms. All trial participants undergo a minor liposuction procedure to remove fat (adipose) tissue. Following the liposuction, trial participants may have their tissue processed with Cytoris proprietary Celution System to separate and concentrate cells, and prepare them for therapeutic use. Trial participants will then have either their own cells or a placebo injected back into their damaged heart tissue. To test whether ADRCs will improve heart function, several measurements will be made, including peak oxygen consumption (VO2max), which measures how much physical exercise (gentle walking on a treadmill) a patient can perform, blood flow to the heart (perfusion), the amount of blood in the left ventricle at the end of contraction and relaxation (end-systolic and end-diastolic volumes), and the fraction of blood that is pumped during each contraction (ejection fraction). After the injection procedure, patients are seen in the clinic for follow-up visits over the first 12 months; they are then contacted by phone once a year for up to five years after the procedure.

There are approximately 5.1 million Americans currently living with heart failure, according to the American Heart Association. Chronic heart failure due to coronary heart disease is a severe, debilitating condition caused by restriction of blood flow to the heart muscle, reducing the hearts oxygen supply and limiting its pumping function. Individuals interested in participating in the ATHENA clinical research trial or learning more can visit http://www.theathenatrial.com or call Brian Nordgren, Florida Hospital Pepin Heart Institute Physician Assistant & Stem Cell Program Lead at (813) 615-7527.

About Florida Hospital Tampa Florida Hospital Tampa is a not-for-profit 475-bed tertiary hospital specializing in cardiovascular medicine, neuroscience, orthopaedics, womens services, pediatrics, oncology, endocrinology, bariatrics, wound healing, sleep medicine and general surgery including minimally invasive and robotic-assisted procedures. Also located at Florida Hospital Tampa is the renowned Florida Hospital Pepin Heart Institute, a recognized leader in cardiovascular disease prevention, diagnosis, treatment and leading-edge research. Part of the Adventist Health System, Florida Hospital is a leading health network comprised of 22 hospitals throughout the state. For more information, visit http://www.FHTampa.org.

About Florida Hospital Pepin Heart Institute and Dr. Kiran C. Patel Research Institute Florida Hospital Pepin Heart Institute is a free-standing cardiovascular institute providing comprehensive cardiovascular care with over 76,000 angioplasty procedures and 11,000 open-heart surgeries in the Tampa Bay region. Leading the way with the first accredited chest pain emergency room in Tampa Bay, the institute is among an elite few in the state of Florida chosen to perform the ground breaking Transcatheter Aortic Valve Replacement (TAVR) procedure. It is also a HeartCaring designated provider and a Larry King Cardiac Foundation Hospital. Florida Hospital Pepin Heart Institute and the Dr. Kiran C. Patel Research Institute, affiliated with the University of South Florida (USF), are exploring and conducting leading-edge research to develop break-through treatments long before they are available in most other hospitals. To learn more, visit http://www.FHPepin.org.

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Groundbreaking Stem Cell Clinical Trial

(PRWEB) December 20, 2013

Florida Hospital Pepin Heart Institute and Dr. Kiran C. Patel Research Institute announced the first patient, a 59 year old Clearwater man, has been treated as part of the ATHENA clinical trial. The trial, sponsored by San Diego-based Cytori Therapeutics, derives stem cells from the patients own fat tissue and injects extracted cells into damaged parts of the heart. The ATHENA trial is a treatment for chronic heart failure due to coronary heart disease. Dr. Charles Lambert, Medical Director of Florida Hospital Pepin Heart Institute, is leading the way for the first U.S. FDA approved clinical trial using adipose-derived regenerative cells, known as ADRCs, in chronic heart failure patients. I am pleased to report that all procedures went well. The patient is doing well, he was released and is recovering at home. We look forward to following his progress over the coming months, said Dr. Charles Lambert.

Heart failure (HF) can occur when the muscles of the heart become weakened and cannot pump blood sufficiently throughout the body. The injury is most often caused by inadequate blood flow to the heart resulting from chronic or acute cardiovascular disease, including heart attacks. The ATHENA clinical trial procedure is a three step process. First, the trial involves the collection of fat from the patients body by liposuction. Then the fat sample is filtered through a machine that extracts out the stem cells. Finally, the stem cells are injected into the damaged part of the patients heart. During this first case at Florida Hospital Pepin Heart Institute, Dr. Paul Smith performed the liposuction to obtain the fat sample, a team at the Dr. Kiran C. Patel Research Institute isolated stem cells from the fat sample and then Dr. Charles Lambert performed the cell therapy by direct injection into the patients heart. Pepin Heart and Dr. Kiran C. Patel Research Institute is exploring and conducting leading-edge research to develop break-through treatments long before they are even available in other facilities. Stem cells have the unique ability to develop into many different cell types, and in many tissues serve as an internal repair system, dividing essentially without limit to replenish other cells, said Dr. Lambert. The Pepin Heart Institute has a history of cardiovascular stem cell research as part of the NIH sponsored Cardiac Cell Therapy Research Network (CCTRN) as well as other active cell therapy trials. The trial is a double blind, randomized, placebo controlled study designed to study the use of a patients own Adipose-Derived Regenerative Cells (ADRCs) to treat chronic heart failure from coronary heart disease in patients who are on maximal therapy and still have heart failure symptoms. All trial participants undergo a minor liposuction procedure to remove fat (adipose) tissue. Following the liposuction, trial participants may have their tissue processed with Cytoris proprietary Celution System to separate and concentrate cells, and prepare them for therapeutic use. Trial participants will then have either their own cells or a placebo injected back into their damaged heart tissue. To test whether ADRCs will improve heart function, several measurements will be made, including peak oxygen consumption (VO2max), which measures how much physical exercise (gentle walking on a treadmill) a patient can perform, blood flow to the heart (perfusion), the amount of blood in the left ventricle at the end of contraction and relaxation (end-systolic and end-diastolic volumes), and the fraction of blood that is pumped during each contraction (ejection fraction). After the injection procedure, patients are seen in the clinic for follow-up visits over the first 12 months; they are then contacted by phone once a year for up to five years after the procedure. There are approximately 5.1 million Americans currently living with heart failure, according to the American Heart Association. Chronic heart failure due to coronary heart disease is a severe, debilitating condition caused by restriction of blood flow to the heart muscle, reducing the hearts oxygen supply and limiting its pumping function. Individuals interested in participating in the ATHENA clinical research trial or learning more can visit http://www.theathenatrial.com or call Brian Nordgren, Florida Hospital Pepin Heart Institute Physician Assistant & Stem Cell Program Lead at (813) 615-7527.

About Florida Hospital Pepin Heart Institute and Dr. Kiran C. Patel Research Institute Florida Hospital Pepin Heart Institute, located at Florida Hospital Tampa, is a free-standing cardiovascular institute providing comprehensive cardiovascular care with over 76,000 angioplasty procedures and 11,000 open-heart surgeries in the Tampa Bay region. Leading the way with the first accredited chest pain emergency room in Tampa Bay, the institute is among an elite few in the state of Florida chosen to perform the ground breaking Transcatheter Aortic Valve Replacement (TAVR) procedure. It is also a HeartCaring designated provider and a Larry King Cardiac Foundation Hospital. Florida Hospital Pepin Heart Institute and the Dr. Kiran C. Patel Research Institute, affiliated with the University of South Florida (USF), are exploring and conducting leading-edge research to develop break-through treatments long before they are available in most other hospitals. To learn more, visit http://www.FHPepin.org

About Cytori Therapeutics Cytori Therapeutics, Inc. is developing cell therapies based on autologous adipose-derived regenerative cells (ADRCs) to treat cardiovascular disease and repair soft tissue defects. Our scientific data suggest ADRCs improve blood flow, moderate the immune response and keep tissue at risk of dying alive. As a result, we believe these cells can be applied across multiple "ischemic" conditions. These therapies are made available to the physician and patient at the point-of-care by Cytori's proprietary technologies and products, including the Celution system product family. http://www.cytori.com

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Florida Hospital Pepin Heart Institute is First in West & Central Florida to Perform a Groundbreaking Stem Cell ...

PUBLIC RELEASE DATE:

16-Dec-2013

Contact: Jennifer Schutz newsbureau@mayo.edu 507-284-5005 Mayo Clinic

ROCHESTER, Minn. -- Mayo Clinic researchers and colleagues in Belgium have developed a specialized catheter for transplanting stem cells into the beating heart. The novel device includes a curved needle and graded openings along the needle shaft, allowing for increased distribution of cells. The result is maximized retention of stem cells to repair the heart. The findings appear in the journal Circulation: Cardiovascular Interventions.

"Although biotherapies are increasingly more sophisticated, the tools for delivering regenerative therapies demonstrate a limited capacity in achieving high cell retention in the heart," says Atta Behfar, M.D., Ph.D., a Mayo Clinic cardiology specialist and lead author of the study. "Retention of cells is, of course, crucial to an effective, practical therapy."

Researchers from the Mayo Clinic Center for Regenerative Medicine in Rochester and Cardio3 Biosciences in Mont-Saint-Guibert, Belgium, collaborated to develop the device, beginning with computer modeling in Belgium. Once refined, the computer-based models were tested in North America for safety and retention efficiency.

What's the significance?

This new catheter is being used in the European CHART-1 clinical trials, now underway. This is the first Phase III trial to regenerate hearts of patients who have suffered heart attack damage. The studies are the outcome of years of basic science research at Mayo Clinic and earlier clinical studies with Cardio3 BioSciences and Cardiovascular Centre in Aalst, Belgium, conducted between 2009 and 2010.

###

The development of the catheter and subsequent studies were supported by Cardio3 BioSciences; Walloon Region General Directorate for Economy, Employment & Research; Meijer Lavino Foundation for Cardiac Research Aalst (Belgium); the National Institutes of Health; Grainger Foundation; Florida Heart Research Institute; Marriott Heart Disease Research Program; and the Mayo Clinic Center for Regenerative Medicine.

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Regenerative medicine: Mayo Clinic and collaborators develop new tool for transplanting stem cells

A new study says heart damage may be reversible with stem cell therapy without dangerous side effects.

STORY HIGHLIGHTS

(CNN) -- On a June day in 2009, a 39-year-old man named Ken Milles lay on an exam table at Cedars-Sinai Medical Center in Los Angeles. A month earlier, he'd suffered a massive heart attack that destroyed nearly a third of his heart.

"The most difficult part was the uncertainty," he recalls. "Your heart is 30% damaged, and they tell you this could affect you the rest of your life." He was about to receive an infusion of stem cells, grown from cells taken from his own heart a few weeks earlier. No one had ever tried this before.

About three weeks later, in Kentucky, a patient named Mike Jones underwent a similar procedure at the University of Louisville's Jewish Hospital. Jones suffered from advanced heart failure, the result of a heart attack years earlier. Like Milles, he received an infusion of stem cells, grown from his own heart tissue.

"Once you reach this stage of heart disease, you don't get better," says Dr. Robert Bolli, who oversaw Jones' procedure, explaining what doctors have always believed and taught. "You can go down slowly, or go down quickly, but you're going to go down."

Conventional wisdom took a hit Monday, as Bolli's group and a team from Cedars-Sinai each reported that stem cell therapies were able to reverse heart damage, without dangerous side effects, at least in a small group of patients.

In Bolli's study, published in The Lancet, 16 patients with severe heart failure received a purified batch of cardiac stem cells. Within a year, their heart function markedly improved. The heart's pumping ability can be quantified through the "Left Ventricle Ejection Fraction," a measure of how much blood the heart pumps with each contraction. A patient with an LVEF of less than 40% is considered to suffer severe heart failure. When the study began, Bolli's patients had an average LVEF of 30.3%. Four months after receiving stem cells, it was 38.5%. Among seven patients who were followed for a full year, it improved to an astounding 42.5%. A control group of seven patients, given nothing but standard maintenance medications, showed no improvement at all.

"We were surprised by the magnitude of improvement," says Bolli, who says traditional therapies, such as placing a stent to physically widen the patient's artery, typically make a smaller difference. Prior to treatment, Mike Jones couldn't walk to the restroom without stopping for breath, says Bolli. "Now he can drive a tractor on his farm, even play basketball with his grandchildren. His life was transformed."

At Cedars-Sinai, 17 patients, including Milles, were given stem cells approximately six weeks after suffering a moderate to major heart attack. All had lost enough tissue to put them "at big risk" of future heart failure, according to Dr. Eduardo Marban, the director of the Cedars-Sinai Heart Institute, who developed the stem cell procedure used there.

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Studies: Stem cells reverse heart damage - CNN.com

Washington, Dec 7 : NASA and the Center for the Advancement of Science in Space (CASIS) are enabling research aboard the International Space Station that could lead to new stem cell-based therapies for medical conditions faced on Earth and in space.

Scientists will take advantage of the space station's microgravity environment to study the properties of non-embryonic stem cells.

NASA is interested in space-based cell research because it is seeking ways to combat the negative health effects astronauts face in microgravity, including bone loss and muscle atrophy.

Mitigation techniques are necessary to allow humans to push the boundaries of space exploration far into the solar system. This knowledge could help people on Earth, particularly the elderly, who are afflicted with similar conditions.

Two stem cell investigations scheduled to fly to the space station next year were highlighted Friday, Dec. 6, at the World Stem Cell Summit in San Diego.

Lee Hood, a member of the CASIS Board of Directors, moderated a panel session in which scientists Mary Kearns-Jonker of Loma Linda University in California and Roland Kaunas of Texas A&M University discussed their planned research, which will gauge the impact of microgravity on fundamental stem cell properties.

Kearns-Jonker's research will study the aging of neonatal and adult cardiac stem cells in microgravity with the ultimate goal of improving cardiac cell therapy.

Kaunas is a part of a team of researchers developing a system for co-culturing and analyzing stem cells mixed with bone tumor cells in microgravity.

This system will allow researchers to identify potential molecular targets for drugs specific to certain types of cancer.

Stem cells are cells that have not yet become specialized in their functions. They display a remarkable ability to give rise to a spectrum of cell types and ensure life-long tissue rejuvenation and regeneration.

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Space Station made accessible for stem cell research

Durham, NC (PRWEB) December 09, 2013

Generating new cardiac muscle from human embryonic stem cells (hESCs) and/or induced pluripotent stem cells (iPSC) could fulfill the demand for therapeutic applications and drug testing. The production of a similar population of these cells remains a major limitation, but in a study just published in STEM CELLS Translational Medicine, researchers now believe they have found a way to do this.

By combining small molecules and growth factors, the international research team led by investigators at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai developed a two-step system that caused stem cells to differentiate into ventricular heart muscle cells from hESCs and iPSCs. The process resulted in high efficiency and reproducibility, in a manner that mimicked the developmental steps of normal cardiovascular development.

These chemically induced, ventricular-like cardiomyocytes (termed ciVCMs) exhibited the expected cardiac electrophysiological and calcium handling properties as well as the appropriate heart rate responses, said lead investigator Ioannis Karakikes, Ph.D., of the Stanford University School Of Medicine, Cardiovascular Institute. Other members of the team included scientists from the Icahn School of Medicine at Mount Sinai, New York, and the Stem Cell & Regenerative Medicine Consortium at the University of Hong Kong.

In addition, using an integrated approach involving computational and experimental systems, the researchers demonstrated that using molecules to modulate the Wnt pathway, which passes signals from cell to cell, plays a key role in whether a cell evolves into an atrial or ventricular muscle cell.

The further clarification of the molecular mechanism(s) that underlie this kind of subtype specification is essential to improving our understanding of cardiovascular development. We may be able to regulate the commitment, proliferation and differentiation of pluripotent stem cells into heart muscle cells and then harness them for therapeutic purposes, Dr. Karakikes said.

"Most cases of heart failure are related to a deficiency of heart muscle cells in the lower chambers of the heart, said said Anthony Atala, MD, editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. An efficient, cost-effective and reproducible system for generating ventricular cardiomyocytes would be a valuable resource for cell therapies as well as drug screening.

###

The full article, Small Molecule-Mediated Directed Differentiation of Human Embryonic Stem Cells Toward Ventricular Cardiomyocytes, can be accessed at http://www.stemcellstm.com.

About STEM CELLS Translational Medicine: STEM CELLS TRANSLATIONAL MEDICINE (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

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More Efficient Way to Grow Heart Muscle from Stem Cells Could Yield New Regenerative Therapies

NASA and the Center for the Advancement of Science in Space (CASIS) are enabling research aboard the International Space Station that could lead to new stem cell-based therapies for medical conditions faced on Earth and in space.

Scientists will take advantage of the space station's microgravity environment to study the properties of non-embryonic stem cells.

NASA is interested in space-based cell research because it is seeking ways to combat the negative health effects astronauts face in microgravity, including bone loss and muscle atrophy. Mitigation techniques are necessary to allow humans to push the boundaries of space exploration far into the solar system. This knowledge could help people on Earth, particularly the elderly, who are afflicted with similar conditions.

Two stem cell investigations scheduled to fly to the space station next year were highlighted Friday, Dec. 6, at the World Stem Cell Summit in San Diego. Lee Hood, a member of the CASIS Board of Directors, moderated a panel session in which scientists Mary Kearns-Jonker of Loma Linda University in California and Roland Kaunas of Texas A&M University discussed their planned research, which will gauge the impact of microgravity on fundamental stem cell properties.

Kearns-Jonker's research will study the aging of neonatal and adult cardiac stem cells in microgravity with the ultimate goal of improving cardiac cell therapy. Kaunas is a part of a team of researchers developing a system for co-culturing and analyzing stem cells mixed with bone tumor cells in microgravity. This system will allow researchers to identify potential molecular targets for drugs specific to certain types of cancer.

Stem cells are cells that have not yet become specialized in their functions. They display a remarkable ability to give rise to a spectrum of cell types and ensure life-long tissue rejuvenation and regeneration. Experiments on Earth and in space have shown that microgravity induces changes in the way stem cells grow, divide and specialize. Stem cell biology in microgravity could inform fields ranging from discovery science to tissue engineering to regenerative medicine.

NASA selected CASIS to maximize use of the International Space Station's U.S. National Laboratory through 2020. CASIS is dedicated to supporting and accelerating innovations and new discoveries that will enhance the health and wellbeing of people and our planet.

For more information about the International Space Station, visit:

http://www.nasa.gov/station

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NASA, CASIS Make Space Station Accessible for Stem Cell Research

An interview with Roberto Bolli, MD.

University of Louisville cardiologist Roberto Bolli, MD, led the stem cell study that tested using patients' own heart stem cells to help their hearts recover from heart failure. Though that trial was preliminary, the results look promising -- and may one day lead to a cure for heart failure.

Here, Bolli talks about what this work means and when it might become an option for patients.

2012 WebMD, LLC. All rights reserved.

"Realistically, this will not come... for another three or four years, at least," Bolli says. "It may be longer, depending on the results of the next trial, of course."

Larger studies are needed to confirm the procedure's safety and effectiveness. If those succeed, it could be "the biggest advance in cardiovascular medicine in my lifetime," Bolli says.

A total of 20 patients took part in the initial study.

All of them experienced significant improvement in their heart failure and now function better in daily life, according to Bolli. "The patients can do more, there's more ability to exercise, and the quality of life improves markedly," Bolli says.

Bolli's team published its findings on how the patients were doing one year after stem cell treatment in November 2011 in the Lancet, a British medical journal.

Each patient was infused with about 1 million of his or her own cardiac stem cells, which could eventually produce an estimated 4 trillion new cardiac cells, Bolli says. His team plans to follow each patient for two years after their stem cell procedure.

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Heart Stem Cell Trial: Interview With Researcher Roberto Bolli, MD

In a small study involving 25 volunteers, stem cell recipients had their heart attack scars reduced most dramatically -- on average almost 50 percent -- damaged muscle replaced by new healthy heart tissue. CBS News

In a small study involving 25 volunteers, stem cell recipients had their heart attack scars reduced most dramatically - on average, 50 percent - and damaged muscle replaced by new healthy heart tissue.

CBS News

(CBS) A new study offers an effective way to mend a broken heart: Stem cells.

PICTURES: 7 heart-healthy foods

The study looked at patients with damaged hearts from myocardial infarctions, or heart attacks, and found stem cells reduced the amount of scarring and helped hearts regrow healthy muscle.

"This discovery challenges the conventional wisdom that, once established, scar is permanent and that, once lost, healthy heart muscle cannot be restored," study co-author Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute and inventor of the techniques used in the procedure, said in a hospital written statement.

For the study, researchers tested 25 patients, an average of 53 years old, who had experienced heart attacks that had left them with damaged heart muscle. Eight patients served as controls and were treated with conventional treatments including medication, and diet and exercise recommendations. The other 17 patients received stem cells, which researchers derived from raisin-sized pieces of patients' own heart tissue.

The researchers found that patients treated with stem cells experienced almost a 50 percent reduction of heart attack scars within 12 months of treatment, while the eight patients who received conventional treatment saw no reductions in damage.

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Stem cells heal heart attack scars, regrow healthy muscle ...

The hearts own stem cells play their part in regeneration

Sca1 stem cells replace steadily ageing heart muscle cells

November 28, 2013

Up until a few years ago, the common school of thought held that the mammalian heart had very little regenerative capacity. However, scientists now know that heart muscle cells constantly regenerate, albeit at a very low rate. Researchers at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, have identified a stem cell population responsible for this regeneration. Hopes are growing that it will be possible in future to stimulate the self-healing powers of patients with diseases and disorders of the heart muscle, and thus develop new potential treatments.

Stem cells play a part in heart regeneration. This image of the fluorescence microscope depicts a section of the heart tissue of a mouse. The green colouring of the cells in the middle shows that the cell originated from a so-called Sca1 stem cell.

MPI for Heart and Lung Research

MPI for Heart and Lung Research

Some vertebrates seem to have found the fountain of youth, the source of eternal youth, at least when it comes to their heart. In many amphibians and fish, for example, this important organ has a marked capacity for regeneration and self-healing. Some species in the two animal groups have even perfected this capability and can completely repair damage caused to heart tissue, thus maintaining the organs full functionality.

The situation is different for mammals, whose hearts have a very low regenerative capacity. According to the common school of thought that has prevailed until recently, the reason for this deficit is that the heart muscle cells in mammals cease dividing shortly after birth. It was also assumed that the mammalian heart did not have any stem cells that could be used to form new heart muscle cells. On the contrary: new studies show that aged muscle cells are also replaced in mammalian hearts. Experts estimate, however, that between just one and four percent of heart muscle cells are replaced every year.

Scientists in Thomas Brauns Research Group at the Max Planck Institute for Heart and Lung Research have succeeded in identifying a stem cell population in mice that plays a key role in this regeneration of heart muscle cells. Experiments conducted by the researchers in Bad Nauheim on genetically modified mice show that the Sca1 stem cells in a healthy heart are involved in the ongoing replacement of heart muscle cells. The Sca-1 cells increase their activity if the heart is damaged, with the result that significantly more new heart muscle cells are formed.

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Research | Research news | 2013 | The heart’s own stem cells ...

By the time Bill Beatty made it to the Emergency Department in Howard County, he was already several hours into a major heart attack. His physicians performed a series of emergency treatments that included an intra-aortic balloon pump, but the 57-year-old engineers blood pressure remained dangerously low. The cardiologist called for a helicopter to transfer him to Johns Hopkins.

It was fortuitous timing: Beatty was an ideal candidate for a clinical trial and soon received an infusion of stem cells derived from his own heart tissue, making him the second patient in the world to undergo the procedure.

Of all the attempts to harness the promise of stem cell therapy, few have garnered more hope than the bid to repair damaged hearts. Previous trials with other stem cells have shown conflicting results. But this new trial, conducted jointly with cardiologist Eduardo Marbn at Cedars-Sinai Medical Center in Los Angeles, is the first time stem cells come from the patients own heart.

Cardiologist Jeffrey Brinker, M.D., a member of the Hopkins team, thinks the new protocol could be a game-changer. That's based partly on recent animal studies in which scientists at both institutions isolated stem cells from the injured animals hearts and infused them back into the hearts of those same animals. The stem cells formed new heart muscle and blood vessel cells. In fact, says Brinker, the new cells have a pre-determined cardiac fate. Even in the culture dish, he says, theyre a beating mass of cells.

Whats more, according to Gary Gerstenblith, M.D., J.D., the animals in these studies showed a significant decrease in relative infarct size, shrinking by about 25 percent. Based on those and earlier findings, investigators were cleared by the FDA and Hopkins Institutional Review Board to move forward with a human trial.

In Beattys case, Hopkins heart failure chief Stuart Russell, M.D., extracted a small sample of heart tissue and shipped it to Cedars Sinai, where stem cells were isolated, cultured and expanded to large numbers. Hopkins cardiologist Peter Johnston, M.D., says cardiac tissue is robust in its ability to generate stem cells, typically yielding several million transplantable cells within two months.

When ready, the cells were returned to Baltimore and infused back into Beatty through a balloon catheter placed in his damaged artery, ensuring target-specific delivery. Then the watching and waiting began. For the Hopkins team, Beattys infarct size will be tracked by imaging chief Joao Lima, M.D., M.B.A.,and his associates using MRI scans.

Now back home and still struggling with episodes of compromised stamina and shortness of breath, Beatty says his Hopkins cardiologists were fairly cautious in their prognosis, but hell be happy for any improvement.

Nurse coordinator Elayne Breton says Beatty is scheduled for follow-up visits at six months and 12 months, when they hope to find an improvement in his hearts function. But at least one member of the Hopkins team was willing acknowledge a certain optimism. The excitement here, says Brinker, is huge.

The trial is expected to be completed within one to two years.

Follow this link:
Stem Cell Research at Johns Hopkins Medicine: Repairing Heart ...

Finished heart switches stem cells off

Transcription factor Ajuba regulates stem cell activity in the heart during embryonic development

July 12, 2012

It is not unusual for babies to be born with congenital heart defects. This is because the development of the heart in the embryo is a process which is not only extremely complex, but also error-prone. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now identified a key molecule that plays a central role in regulating the function of stem cells in the heart. As a result, not only could congenital heart defects be avoided in future, but new ways of stimulating the regeneration of damaged hearts in adults may be opened up.

Cardiac development out of control: Absence of the transcription factor Ajuba during cardiac development, as is the case in the right-hand photo due to genetic intervention, disrupts development of the heart in the fish embryo. In addition to an increased number of cardiac muscle cells (green with red-stained nuclei), the heart is additionally deformed during development.

Max Planck Institute for Heart and Lung Research

Max Planck Institute for Heart and Lung Research

It's a long road from a cluster of cells to a finished heart. Cell division transforms what starts out as a collection of only a few cardiac stem cells into an ever-larger structure from which the various parts of the heart, such as ventricles, atria, valves and coronary vessels, develop. This involves the stem and precursor cells undergoing a complex process which, in addition to tightly regulated cell division, also includes cell migration, differentiation and specialisation. Once the heart is complete, the stem cells are finally switched off.

Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now discovered how major parts of this development process are regulated. Their search initially focused on finding binding partners for transcription factor Isl1. Isl1 is characteristic of a specific group of cardiac stem cells which are consequently also known as Isl1+ cells. During their search, the researchers came across Ajuba, a transcription factor from the group of LIM proteins. "We then took a closer a look at the interaction between these two molecules and came to the conclusion that Ajuba must be an important switch", says Gergana Dobreva, head of the "Origin of Cardiac Cell Lineages" Research Group at the Bad Nauheim-based Max Planck Institute.

Using an animal model, the scientists then investigated the effects of a defective switch on cardiac development. Embryonic development can be investigated particularly effectively in the zebrafish. The Bad Nauheim-based researchers therefore produced a genetically modified fish that lacked a functioning Ajuba protein. Cardiac development in these fishes was in fact severely disrupted. In addition to deformation of the heart, caused by twisting of the cardiac axis, what particularly struck the researchers was a difference in size in comparison with control animals. "In almost all the investigated fish we observed a dramatic enlargement of the heart. If Ajuba is absent, there is clearly no other switch that finally silences the Isl1-controlled part of cardiac development", says Dobreva.

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Research | Research news | 2012 | Finished heart switches stem ...

[International version] Linda van Laake: "We want to work together to improve stem cell treatment"
Dr Linda van Laake is assistant professor and specialist registrar in Cardiology at the University Medical Center Utrecht and Hubrecht Institute. She carries...

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[International version] Linda van Laake: "We want to work together to improve stem cell treatment" - Video

[International version] Linda van Laake: "We want to work together to improve stem cell treatment"
Dr Linda van Laake is assistant professor and specialist registrar in Cardiology at the University Medical Center Utrecht and Hubrecht Institute. She carries...

By: UniversiteitUtrecht

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[International version] Linda van Laake: "We want to work together to improve stem cell treatment" - Video

Charles A. Goldthwaite, Jr., Ph.D.

Cardiovascular disease (CVD), which includes hypertension, coronary heart disease (CHD), stroke, and congestive heart failure (CHF), has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic.1 In 2002, CVD claimed roughly as many lives as cancer, chronic lower respiratory diseases, accidents, diabetes mellitus, influenza, and pneumonia combined. According to data from the 19992002 National Health and Nutrition Examination Survey (NHANES), CVD caused approximately 1.4 million deaths (38.0 percent of all deaths) in the U.S. in 2002. Nearly 2600 Americans die of CVD each day, roughly one death every 34 seconds. Moreover, within a year of diagnosis, one in five patients with CHF will die. CVD also creates a growing economic burden; the total health care cost of CVD in 2005 was estimated at $393.5 billion dollars.

Given the aging of the U.S. population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes,2,3 CVD will continue to be a significant health concern well into the 21st century. However, improvements in the acute treatment of heart attacks and an increasing arsenal of drugs have facilitated survival. In the U.S. alone, an estimated 7.1 million people have survived a heart attack, while 4.9 million live with CHF.1 These trends suggest an unmet need for therapies to regenerate or repair damaged cardiac tissue.

Ischemic heart failure occurs when cardiac tissue is deprived of oxygen. When the ischemic insult is severe enough to cause the loss of critical amounts of cardiac muscle cells (cardiomyocytes), this loss initiates a cascade of detrimental events, including formation of a non-contractile scar, ventricular wall thinning (see Figure 6.1), an overload of blood flow and pressure, ventricular remodeling (the overstretching of viable cardiac cells to sustain cardiac output), heart failure, and eventual death.4 Restoring damaged heart muscle tissue, through repair or regeneration, therefore represents a fundamental mechanistic strategy to treat heart failure. However, endogenous repair mechanisms, including the proliferation of cardiomyocytes under conditions of severe blood vessel stress or vessel formation and tissue generation via the migration of bone-marrow-derived stem cells to the site of damage, are in themselves insufficient to restore lost heart muscle tissue (myocardium) or cardiac function.5 Current pharmacologic interventions for heart disease, including beta-blockers, diuretics, and angiotensin-converting enzyme (ACE) inhibitors, and surgical treatment options, such as changing the shape of the left ventricle and implanting assistive devices such as pacemakers or defibrillators, do not restore function to damaged tissue. Moreover, while implantation of mechanical ventricular assist devices can provide long-term improvement in heart function, complications such as infection and blood clots remain problematic.6 Although heart transplantation offers a viable option to replace damaged myocardium in selected individuals, organ availability and transplant rejection complications limit the widespread practical use of this approach.

Figure 6.1. Normal vs. Infarcted Heart. The left ventricle has a thick muscular wall, shown in cross-section in A. After a myocardial infarction (heart attack), heart muscle cells in the left ventricle are deprived of oxygen and die (B), eventually causing the ventricular wall to become thinner (C).

2007 Terese Winslow

The difficulty in regenerating damaged myocardial tissue has led researchers to explore the application of embryonic and adult-derived stem cells for cardiac repair. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells, mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated to varying extents as possible sources for regenerating damaged myocardium. All have been tested in mouse or rat models, and some have been tested in large animal models such as pigs. Preliminary clinical data for many of these cell types have also been gathered in selected patient populations.

However, clinical trials to date using stem cells to repair damaged cardiac tissue vary in terms of the condition being treated, the method of cell delivery, and the primary outcome measured by the study, thus hampering direct comparisons between trials.7 Some patients who have received stem cells for myocardial repair have reduced cardiac blood flow (myocardial ischemia), while others have more pronounced congestive heart failure and still others are recovering from heart attacks. In some cases, the patient's underlying condition influences the way that the stem cells are delivered to his/her heart (see the section, quot;Methods of Cell Deliveryquot; for details). Even among patients undergoing comparable procedures, the clinical study design can affect the reporting of results. Some studies have focused on safety issues and adverse effects of the transplantation procedures; others have assessed improvements in ventricular function or the delivery of arterial blood. Furthermore, no published trial has directly compared two or more stem cell types, and the transplanted cells may be autologous (i.e., derived from the person on whom they are used) or allogeneic (i.e., originating from another person) in origin. Finally, most of these trials use unlabeled cells, making it difficult for investigators to follow the cells' course through the body after transplantation (see the section quot;Considerations for Using These Stem Cells in the Clinical Settingquot; at the end of this article for more details).

Despite the relative infancy of this field, initial results from the application of stem cells to restore cardiac function have been promising. This article will review the research supporting each of the aforementioned cell types as potential source materials for myocardial regeneration and will conclude with a discussion of general issues that relate to their clinical application.

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6. Mending a Broken Heart: Stem Cells and Cardiac Repair [Stem ...

Nov. 28, 2013 Up until a few years ago, the common school of thought held that the mammalian heart had very little regenerative capacity. However, scientists now know that heart muscle cells constantly regenerate, albeit at a very low rate. Researchers at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, have identified a stem cell population responsible for this regeneration. Hopes are growing that it will be possible in future to stimulate the self-healing powers of patients with diseases and disorders of the heart muscle, and thus develop new potential treatments.

Some vertebrates seem to have found the fountain of youth, the source of eternal youth, at least when it comes to their heart. In many amphibians and fish, for example, this important organ has a marked capacity for regeneration and self-healing. Some species in the two animal groups have even perfected this capability and can completely repair damage caused to heart tissue, thus maintaining the organ's full functionality.

The situation is different for mammals, whose hearts have a very low regenerative capacity. According to the common school of thought that has prevailed until recently, the reason for this deficit is that the heart muscle cells in mammals cease dividing shortly after birth. It was also assumed that the mammalian heart did not have any stem cells that could be used to form new heart muscle cells. On the contrary: new studies show that aged muscle cells are also replaced in mammalian hearts. Experts estimate, however, that between just one and four percent of heart muscle cells are replaced every year.

Scientists in Thomas Braun's Research Group at the Max Planck Institute for Heart and Lung Research have succeeded in identifying a stem cell population in mice that plays a key role in this regeneration of heart muscle cells. Experiments conducted by the researchers in Bad Nauheim on genetically modified mice show that the Sca1 stem cells in a healthy heart are involved in the ongoing replacement of heart muscle cells. The Sca-1 cells increase their activity if the heart is damaged, with the result that significantly more new heart muscle cells are formed.

Since, in comparison to the large amount of heart muscle cells, Sca-1 stem cells account for just a tiny proportion of the cells in the heart muscle, searching for them is like searching for a needle in a haystack. "We also faced the problem that Sca-1 is no longer available in the cells as a marker protein for stem cells after they have been changed into heart muscle cells. To prove this, we had to be inventive," says project leader Shizuka Uchida. The Max Planck researchers genetically modified the stem cells to such an extent that, in addition to the Sca-1, they produced another visible marker. Even if Sca-1 was subsequently no longer visible, the marker could still be detected permanently.

"In this way, we were able to establish that the proportion of heart muscle cells originating from Sca-1 stem cells increased continuously in healthy mice. Around five percent of the heart muscle cells regenerated themselves within 18 months," says Uchida. Moreover, mice suffering from heart disease triggered by the experiment had up to three times more of these newly formed heart muscle cells.

"The data shows that, in principle, the mammalian heart is able to trigger regeneration and renewal processes. Under normal circumstances, however, these processes are not enough to ultimately repair cardiac damage," says Braun. The aim is to find ways in which the formation of new heart muscle cells from heart stem cells can be improved and thereby strengthen the heart's self-healing powers.

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The heart's own stem cells play their part in regeneration

Abstract

Cardiovascular disease (CVD) continues to be one of the main causes of death in the western world. A high burden of disease and the high costs for the healthcare systems claim for novel therapeutic strategies besides current conventional medical care. One decade ago first clinical trials addressed stem cell based therapies as a potential alternative therapeutic strategy for myocardial regeneration and repair. Besides bone marrow derived stem cells (BMCs), adult stem cells from adipose or cardiac tissue have been used in current clinical studies with inconsistent results. Although outcomes in terms of safety and feasibility are generally encouraging, functional improvements were mostly disappointingly low and have failed to reach expectations. In the future, new concepts for myocardial regeneration, especially concerning recovery of cardiomyocyte loss, have to be developed. Transplantation of novel stem or progenitor cell populations with true regenerative potential, direct reprogramming of scar tissue into functional myocardium, tissue engineering or stimulation of endogenous cardiac repair by pharmacological agents are conceivable. This review summarizes current evidence of stem cell based regenerative therapies and discusses future strategies to improve functional outcomes.

KEYWORDS : Myocardial infarction, regenerative medicine, stem cells, tissue engineering, reprogramming

In 2009 cardiovascular disease (CVD) still accounted for 32.3% of all deaths in the United States and therefore continues to be one of the main causes of death (1). From 1999 to 2009, the rate of death due to CVD has declined, but nevertheless the burden of disease remains high. Although improved medical care and acute management of myocardial infarction have led to a considerable reduction of early mortality rate survivors are susceptible to an increased prevalence of chronic heart failure as they develop scarring followed by ventricular remodeling despite optimum medical care (2,3).

Interestingly, cardiovascular operations and interventional procedures increased by 28% from 2000 to 2010 implicating an enormous cost factor for the healthcare system (1). For 2009, it was estimated that the direct and indirect costs of CVD and stroke add up to about $312.6 billion in the United States, which was more than for any other diagnostic group (1).

The main issue of current pharmacological, interventional or operative therapies is their disability to compensate the irreversible loss of functional cardiomyocytes (4). Hence, the future challenge of cardiovascular therapies will be the functional regeneration of myocardial contractility by novel concepts, like cell based therapy, tissue engineering or reprogramming of scar fibroblasts (5,6).

After promising preclinical results using adult stem and precursor cells for cardiac regeneration a rapid clinical translation using autologous bone marrow cells (BMCs) in patients was initiated (7,8). In the last few years numerous clinical trials addressing the transplantation of various adult stem cell populations for cardiac regeneration have been performed. Essential characteristics for the selected adult stem cell populations are the potential to proliferate, migrate and the ability to transdifferentiate into various mature cell types (9). Today, different adult stem cell sources like BMCs, myocardium or adipose tissue derived cells were already used in clinical trials. Beside direct intracoronary or intramyocardial transplantation of adult stem cells into the heart mobilization of autologous progenitor cells by administration of different cytokines [i.e., erythropoietin (EPO) or granulocyte colony stimulating factor (G-CSF)] were also evaluated in first clinical trials (summarized in and ,).

Regenerative therapies and cell sources currently administered in clinical trials. Current clinical trials use BMCs, ADRCs or CPCs to regenerate impaired myocardium after ischemic events. Alternatively cytokines like EPO or G-CSF are employed to mobilize ...

Transplantation of adult stem cells-clinical trials mentioned in the text.

Mobilization of adult stem cells-clinical trials mentioned in the text.

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Cardiac regeneration: current therapies—future concepts