Volume 9, Issue 1 Summary

A groundbreaking study on repairing damaged heart tissue through stem cell therapy has given patients hope that they may again live active lives. An international team of Mayo Clinic researchers and collaborators has done it by discovering a way to regenerate heart tissue.

Clinical trial participant Miroslav Dlacic near his home in Belgrade.

Andre Terzic, M.D., Ph.D., is the Michael S. and Mary Sue Shannon Family Director, Center for Regenerative Medicine, and the Marriott Family Professor of Cardiovascular Diseases Research at Mayo Clinic in Minnesota.

Miroslav Dlacic's heart attack changed his life drastically and seemingly forever. His damaged heart made him too tired to work in his garden or to spend much time at his leather-accessories workshop in Belgrade, Serbia. Like many patients with heart problems, Dlacic, who is 71, thought he would live his remaining years in a weakened condition.

Then, a groundbreaking Mayo Clinic trial of stem cell therapy to repair damaged heart tissue changed his life again this time for the better.

Dlacic agreed to participate in the Mayo Clinic stem cell trial through the hospital in Serbia where he is treated. Two years later, Dlacic is able to walk again without becoming worn out.

"I am more active, more peppy," he says. "I feel quite well."

"It's a paradigm shift," says Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Center for Regenerative Medicine and senior investigator of the stem cell trial. "We are moving from traditional medicine, which addresses the symptoms of disease, to being legitimately able to cure disease."

For decades, treating patients with cardiac disease has typically involved managing heart damage with medication. It's a bit like driving a car without fixing a sluggish engine you manage the consequences as best you can and learn to live with them.

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Regenerating heart tissue through stem cell therapy ...

Category: Science & Technology Posted: October 3, 2014 01:55PM Author: Guest_Jim_*

Heart attacks are pretty serious and something very hard to recover from, in part because heart cells do not multiply and there are few cardiac muscle stem cells to repair the damage. Cardiac patches have been created to replace damaged cells, but because of how they are made, these patches can cause their own health problems. Researchers at Tel Aviv University have recently developed a new hybrid patch that could address those problems.

Traditionally the patches are made by growing cardiac tissue on a collagen scaffold from pig hearts. One of the problems with this approach is the potential for antigens that will trigger an immune response, causing the patient's body to attack the patch. To get around this the researchers instead harvest fatty tissue from the patient's stomach, as the body will not attack its own cells. This left an issue with connectivity, as the cells in the patch must respond to the electrical signals of the heart, and engineered patches do not immediately form the necessary connections. The solution the researchers tried was to deposit gold nanoparticles onto the cardiac tissue, providing the needed conductivity.

So far the nonimmunogenic hybrid patch has shown itself to transfer electrical signals faster and more efficiently than scaffolds without the gold nanoparticles, when tested in animals. The next step for the technology is to test it in larger animals, and eventually perform clinical trials.

Source: American Friends of Tel Aviv University

Link:
Gold Nanoparticles Used to Improve Cardiac Patches

Stem Cell Therapy: Helping the Body Heal Itself

Stem cells are natures own transformers. When the body is injured, stem cells travel the scene of the accident. Some come from the bone marrow, a modest number of others, from the heart itself. Additionally, theyre not all the same. There, they may help heal damaged tissue. They do this by secreting local hormones to rescue damaged heart cells and occasionally turning into heart muscle cells themselves. Stem cells do a fairly good job. But they could do better for some reason, the heart stops signaling for heart cells after only a week or so after the damage has occurred, leaving the repair job mostly undone. The partially repaired tissue becomes a burden to the heart, forcing it to work harder and less efficiently, leading to heart failure.

Initial research used a patients own stem cells, derived from the bone marrow, mainly because they were readily available and had worked in animal studies. Careful study revealed only a very modest benefit, so researchers have moved on to evaluate more promising approaches, including:

No matter what you may read, stem cell therapy for damaged hearts has yet to be proven fully safe and beneficial. It is important to know that many patients are not receiving the most current and optimal therapies available for their heart failure. If you have heart failure, and wondering about treatment options, an evaluation or a second opinion at a Center of Excellence can be worthwhile.

Randomized clinical trials evaluating these different approaches typically allow enrollment of only a few patients from each hospital, and hence what may be available at the Cleveland Clinic varies from time to time. To inquire about current trials, please call 866-289-6911 and speak to our Resource Nurses.

Cleveland Clinic is a large referral center for advanced heart disease and heart failure we offer a wide range of therapies including medications, devices and surgery. Patients will be evaluated for the treatments that best address their condition. Whether patients meet the criteria for stem cell therapy or not, they will be offered the most advanced array of treatment options.

Allogenic: from one person to another (for example: organ transplant)

Autogenic: use of one's own tissue

Myoblasts: immature muscle cells, may be able to change into functioning heart muscle cells

Stem Cells: cells that have the ability to reproduce, generate new cells, and send signals to promote healing

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Stem-Cell Therapy and Repair after Heart Attack and Heart ...

Freeport, Grand Bahama (PRWEB) October 02, 2014

Dr. Todd K. Malan, M.D., presented to the Grand Bahama Medical & Dental Association 14th Annual Scientific Educational Conference on the science, safety and efficacy of adipose- (fat) derived stem and regenerative cells (ADRCs) for ischemic heart disease and other unmet healthcare needs.

"It was an honor to participate in this conference with medical leadership that values this technology and works so tirelessly to serve the people of Grand Bahama," said Dr. Todd Malan." It is an opportunity for us to work closely with local doctors to improve the quality and standards of care for all patients."

Dr. Malan explained the interrelationship between tissue ischemia, inflammation, autoimmune response and cell death and how ADRCs have combined mechanisms known to assist in repairing multi-factorial illnesses associated with those issues.

According to Malan,The procedure begins with the extraction of a persons body fat, a process done using advanced water-assisted liposuction technology. The persons own adult stem cells are then separated from the fat tissue using a European Union-approved cell processing device."

Immediately following this, the cardiologist injects these cells into and around the low blood flow regions of the heart via a cathetera protocol which allows for better targeting of the cells to repair damaged heart tissue.

Adult stem cell therapy for heart disease is emerging as a new alternative for patients with severe heart conditions who want to live a normal life but are restricted in activities they can no longer do.

"As a leader in providing cell therapy, Okyanos is very excited to bring this innovative treatment to patients in a near-shore, regulated jurisdiction with a new standard of care, said Matt Feshbach, CEO of Okyanos. We welcome the opportunity to help those patients with limited options a chance to live a normal life.

Offering this minimally invasive adult stem cell treatment in their new cardiac catherization lab, Okyanos is scheduled to open in October in Freeport, Grand Bahama.

About Okyanos Heart Institute: (Oh key AH nos)

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Okyanos Presents the Science, Safety, and Efficacy of Adult Stem Cell Therapy

Because heart cells cannot multiply and cardiac muscles contain few stem cells, heart tissue is unable to repair itself after a heart attack. Now Tel Aviv University researchers are literally setting a new gold standard in cardiac tissue engineering.

Dr. Tal Dvir and his graduate student Michal Shevach of TAU's Department of Biotechnology, Department of Materials Science and Engineering, and Center for Nanoscience and Nanotechnology, have been developing sophisticated micro- and nanotechnological tools -- ranging in size from one millionth to one billionth of a meter -- to develop functional substitutes for damaged heart tissues. Searching for innovative methods to restore heart function, especially cardiac "patches" that could be transplanted into the body to replace damaged heart tissue, Dr. Dvir literally struck gold. He and his team discovered that gold particles are able to increase the conductivity of biomaterials.

In a study published by Nano Letters, Dr. Dvir's team presented their model for a superior hybrid cardiac patch, which incorporates biomaterial harvested from patients and gold nanoparticles. "Our goal was twofold," said Dr. Dvir. "To engineer tissue that would not trigger an immune response in the patient, and to fabricate a functional patch not beset by signalling or conductivity problems."

A scaffold for heart cells

Cardiac tissue is engineered by allowing cells, taken from the patient or other sources, to grow on a three-dimensional scaffold, similar to the collagen grid that naturally supports the cells in the heart. Over time, the cells come together to form a tissue that generates its own electrical impulses and expands and contracts spontaneously. The tissue can then be surgically implanted as a patch to replace damaged tissue and improve heart function in patients.

According to Dr. Dvir, recent efforts in the scientific world focus on the use of scaffolds from pig hearts to supply the collagen grid, called the extracellular matrix, with the goal of implanting them in human patients. However, due to residual remnants of antigens such as sugar or other molecules, the human patients' immune cells are likely to attack the animal matrix.

In order to address this immunogenic response, Dr. Dvir's group suggested a new approach. Fatty tissue from a patient's own stomach could be easily and quickly harvested, its cells efficiently removed, and the remaining matrix preserved. This scaffold does not provoke an immune response.

Using gold to create a cardiac network

The second dilemma, to establish functional network signals, was complicated by the use of the human extracellular matrix. "Engineered patches do not establish connections immediately," said Dr. Dvir. "Biomaterial harvested for a matrix tends to be insulating and thus disruptive to network signals."

At his Laboratory for Tissue Engineering and Regenerative Medicine, Dr. Dvir explored the integration of gold nanoparticles into cardiac tissue to optimize electrical signaling between cells. "To address our electrical signalling problem, we deposited gold nanoparticles on the surface of our patient-harvested matrix, 'decorating' the biomaterial with conductors," said Dr. Dvir. "The result was that the nonimmunogenic hybrid patch contracted nicely due to the nanoparticles, transferring electrical signals much faster and more efficiently than non-modified scaffolds."

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A heartbeat away? Hybrid 'patch' could replace transplants

Frankfurt, Germany (PRWEB) September 19, 2014

The Translational Research Institute TRI Medical announced today that its new ND Infusion Catheter is being used in a first-in-man procedure at the University of Frankfurt.

The study commenced on September 4th, 2014 at the University of Frankfurt, Department of Cardiology. The use of the new catheter demonstrated a number of advancements in the delivery of regenerative therapeutics, commonly known as stem cells. We are at the forefront of revolutionizing stem cell delivery to the heart, TRI Medicals Nabil Dib, MD, Msc, offered. The ND Infusion Catheter provides safety and potential efficacy. The catheter also reduces the procedure time to approximately 15 minutes; enabling patients to walk and resume activities in about 2 hours, Dr. Dib continued.

The renowned German Cardiology Center at the University of Frankfurt has extensive experience with the development of cardiac cell-based regenerative therapeutics. Prof. Dr. Andreas M. Zeiher, Chairman of the Department of Cardiology at the University of Frankfurt stated The catheter provides the unique potential to precisely regulate coronary blood flow, while administering cells directly into the heart thus improving safety and potentially efficacy. The innovative design of the catheter's balloon accommodates different vessel sizes, avoiding the need to use multiple catheters, reducing potential risks associated with exchanging the balloon catheter when treating different coronary arteries in an individual patient.

Prior to the first-in-man procedure, extensive cell compatibility testing of bone marrow derived cells with the ND Infusion Catheter revealed that the catheter preserved cell viability and functionality, Stefanie Dimmeler, PhD and Director of the Institute of Cardiovascular Regeneration, Centre of Molecular Medicine stated. The testing proved that the cells are compatible with the ND Infusion Catheter. We see this as potential improvements in safety and clinical outcomes related to cell function and efficacy in patients, Dr. Dimmeler offered.

Safety was top-of-mind when we initiated the first-in-man procedure in Frankfurt. We are elated to report that the procedures outcomes were successful, Dr. Dib stated. Earlier studies revealed that the ND Infusion Catheter reduces cellular clumping, preserves cell viability, improves dispersion and reduces radial forces on the vessel walls during balloon inflation; which collectively might improve patient safety and clinical outcomes.

TRI Medicals Ron Anson, Vice President of Business Development shared The catheters unique design features provide physicians with a valuable new tool in the delivery of specified fluids such as stem cells. We expect to see significant growth in the stem cell research marketplace for the new, state-of-the-art ND Infusion Catheter.

ABOUT TRI Medical TRI Medical is a privately held, medical device development company. TRI Medical is dedicated to providing a pathway to regulatory approval that is efficient, predictable and cost effective.

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Media inquiries regarding TRI Medical, its capabilities and for additional information regarding the ND Infusion Catheter contact: DeAnn Dana Phone: 480.309.2884 Email: DDana(at)TRImedical.com TRI Medical website: http://www.trimedical.com

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First-in-man procedure utilizes a new method of stem cell delivery

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Study Links Sex Hormone Levels in the Blood to Risk of Sudden Cardiac Arrest Measuring the levels of sex hormones in patients blood may identify patients likely to suffer a sudden cardiac arrest, a heart rhythm disorder that is fatal in 95 percent of patients. A new study, published online by the peer-reviewed journal Heart Rhythm, shows that lower levels of testosterone, the predominant male sex hormone, were found in men who had a sudden cardiac arrest. Higher levels of estradiol, the major female sex hormone, were strongly associated with greater chances of having a sudden cardiac arrest in both men and women. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Cedars-Sinai Shortens Premature Infants Intensive Care Stays by 21 Percent in Past Three Years The amount of time premature babies spend in Cedars-Sinais Neonatal Intensive Care Unit, part of the Maxine Dunitz Childrens Health Center, has declined dramatically during the past three years, with the average length of stay dropping from 21 days to 17 days. In recent years there have been some notable medical advances, such as personalized nutrition therapy that helps the smallest infants gain weight, nonsurgical procedures to heal heart defects and new medical protocols for mothers likely to deliver a premature infant. All have contributed to more rapidly improving the health of premature infants and shortening the infants hospital stays. But one of the main reasons for the shorter hospitalizations is a renewed emphasis on coordinating each babys various and complex health needs. CONTACT: Soshea Leibler, 213-215-8000; Email soshea.leibler@cshs.org

Combining Antibodies, Iron Nanoparticles and Magnets Steers Stem Cells to Injured Organs Researchers at the Cedars-Sinai Heart Institute infused antibody-studded iron nanoparticles into the bloodstream to treat heart attack damage. The combined nanoparticle enabled precise localization of the bodys own stem cells to the injured heart muscle. The study, which focused on laboratory rats, was published in the online peer reviewed journal Nature Communications. The study addresses a central challenge in stem cell therapeutics: how to achieve targeted interactions between stem cells and injured cells. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Cedars-Sinai Presents Educational Program on Pituitary Disorders for Patients and Families Disorders of the pituitary gland often cause gradual onset of challenging and difficult-to-manage symptoms, and it is not uncommon for patients to consult doctor after doctor in search of an accurate diagnosis and the hope of treatment. In a one-day conference in Huntington Beach on Sept. 28, pituitary experts from Cedars-Sinai will provide an update for patients and their families on the most recent advances in the diagnosis and treatment of pituitary disorders. Patients will be able to engage in discussions and Q&A sessions with the faculty. CONTACT: Sandy Van, 808-526-1708; Email sandy@prpacific.com

Researchers Developing Noninvasive Method for Diagnosing Common, Painful Back Condition An interdisciplinary research team in the Cedars-Sinai Biomedical Imaging Research Institute, Department of Biomedical Sciences, Regenerative Medicine Institute and Department of Surgery received a grant from the National Institutes of Health (NIH) to develop the first imaging technique used to identify biomarkers that could indicate patients have a painful, degenerative back condition. Biomarkers are certain body substances, such as proteins or body fluids that can indicate specific health conditions. When noninvasive imaging procedures can identify exactly where the biomarkers are, researchers may alleviate the need for painful and invasive diagnostic procedures and, in the future, provide targeted, stem cell-based therapies to patients with the condition. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org

Cedars-Sinais New Comprehensive Transplant Center Opens The new home of the Cedars-Sinai Comprehensive Transplant Center opens Monday and consolidates the clinical and administrative services for liver, kidney, lung and pancreas transplant patients. The four programs were previously housed at several locations on the 24-acre medical center campus, but now transplant patients can have nearly all of their medical needs addressed at one location. The three-story facility covers 36,500 square feet and is located at 8900 Beverly Blvd., two blocks from the main medical center campus. The new center has 22 exam rooms, infusion therapy and phlebotomy services, patient education space and an outpatient procedure room. Two floors of underground parking and valet parking service are available to patients and their families. (High resolution photos available upon request) CONTACT: Laura Coverson, 310-423-5215; Email laura.coverson@cshs.org

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Cedars-Sinai Medical Tip Sheet for Sept. 2014

PUBLIC RELEASE DATE:

10-Sep-2014

Contact: Sally Stewart sally.stewart@cshs.org 310-248-6566 Cedars-Sinai Medical Center

LOS ANGELES Researchers at the Cedars-Sinai Heart Institute infused antibody-studded iron nanoparticles into the bloodstream to treat heart attack damage. The combined nanoparticle enabled precise localization of the body's own stem cells to the injured heart muscle.

The study, which focused on laboratory rats, was published today in the online peer reviewed journal Nature Communications. The study addresses a central challenge in stem cell therapeutics: how to achieve targeted interactions between stem cells and injured cells.

Although stem cells can be a potent weapon in the fight against certain diseases, simply infusing a patient with stem cells is no guarantee the stem cells will be able to travel to the injured area and work collaboratively with the cells already there.

"Infusing stem cells into arteries in order to regenerate injured heart muscle can be inefficient," said Eduardo Marbn, MD, PhD, director of the Cedars-Sinai Heart Institute, who led the research team. "Because the heart is continuously pumping, the stem cells can be pushed out of the heart chamber before they even get a chance to begin to heal the injury."

In an attempt to target healing stem cells to the site of the injury, researchers coated iron nanoparticles with two kinds of antibodies, proteins that recognize and bind specifically to stem cells and to injured cells in the body. After the nanoparticles were infused into the bloodstream, they successfully tracked to the injured area and initiated healing.

"The result is a kind of molecular matchmaking," Marbn said. "Through magnetic resonance imaging, we were able to see the iron-tagged cells traveling to the site of injury where the healing could begin. Furthermore, targeting was enhanced even further by placing a magnet above the injured heart."

The Cedars-Sinai Heart Institute has been at the forefront of developing investigational stem cell treatments for heart attack patients. In 2009, Marbn and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and regrow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle.

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Combining antibodies, iron nanoparticles and magnets steers stem cells to injured organs

Kotlikoff lab

Optogenetic proteins enable visualization of a developing heart.

New technologies involving optogenetic proteins, which use light to control and observe cells with unprecedented precision, have begun to illuminate processes underlying cellular behavior and the effects of cell- and gene-based therapies. Cornell researchers are developing advanced forms of these proteins to create a toolkit to make them more widely available to scientists.

With a five-year, $3.1 million grant from the National Institutes of Healths Heart, Lung and Blood Institute, the team will develop the Cornell Heart, Lung and Blood Resource for Optogenetic Mice (CHROMus), which will incorporate optogenetic proteins in mice and human stem cells. Scientists use such tools to control and observe how different types of cells function and interact.

We will target these tools so that they can be combined to study diseases of the heart, lungs, vasculature and blood, said Dr. Michael Kotlikoff, the Austin O. Hooey Dean of Veterinary Medicine at Cornells College of Veterinary Medicine and the projects lead investigator. Researchers will be able to use them to address a broad set of health issues, including heart attack, stroke, asthma and immune diseases.

Marrying optics and genetics, optogenetics enables scientists to use light to trigger and monitor the behavior of cells engineered to contain one or both of two types of designer proteins: effectors, which respond to light by activating the cell they are on, or sensors, which fluoresce when a cell has been activated.

Effectors and sensors can be engineered into specific kinds of cells and color-coded, letting scientists noninvasively trigger one type to see how another type responds. One can see different cell types light up in living animals, giving direct insight into specific cells roles in complex biological systems.

The lines of CHROMus mice developed in this project are designed to be easily crossbred, creating a combinatorial platform that will allow scientists to customize sets of effectors and sensors including new sensors from the Kotlikoff lab into the specific cell types they want to study.

For example, our lab is particularly interested in using these tools to study the control of blood flow to tissues what happens before, during and after major events like stroke and cardiac infarction, and how abnormal rhythms develop after heart injury, said Kotlikoff. Arrhythmias following a heart attack are the single most common cause of acute death in the western world, and how they can be prevented requires a better understanding of how, why and where they arise. Optogenetic tools let us look directly at relevant cells throughout the heart to determine their role in these dangerous and often fatal events.

The tools will be designed to allow scientists to ask and answer similar questions related to vascular and lung diseases, such as the role of the immune system in asthma and stroke, and how therapeutic stem cells integrate within the tissue that they are designed to repair.

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Optogenetics shed light on cardiac, lung, immune disease

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What if repairing large segments of damaged muscle tissue was as simple as mobilizing the body's stem cells to the site of the injury? New research in mice and rats, conducted at Wake Forest Baptist Medical Center's Institute for Regenerative Medicine, suggests that "in body" regeneration of muscle tissue might be possible by harnessing the body's natural healing powers.

Reporting online ahead of print in the journal Acta Biomaterialia, the research team demonstrated the ability to recruit stem cells that can form muscle tissue to a small piece of biomaterial, or scaffold that had been implanted in the animals' leg muscle. The secret to success was using proteins involved in cell communication and muscle formation to mobilize the cells.

"Working to leverage the body's own regenerative properties, we designed a muscle-specific scaffolding system that can actively participate in functional tissue regeneration," said Sang Jin Lee, Ph.D., assistant professor of regenerative medicine and senior author. "This is a proof-of-concept study that we hope can one day be applied to human patients."

The current treatment for restoring function when large segments of muscle are injured or removed during tumor surgery is to surgically move a segment of muscle from one part of the body to another. Of course, this reduces function at the donor site.

Several scientific teams are currently working to engineer replacement muscle in the lab by taking small biopsies of muscle tissue, expanding the cells in the lab, and placing them on scaffolds for later implantation. This approach requires a biopsy and the challenge of standardizing the cells.

"Our aim was to bypass the challenges of both of these techniques and to demonstrate the mobilization of muscle cells to a target-specific site for muscle regeneration," said Lee.

Most tissues in the body contain tissue-specific stem cells that are believed to be the "regenerative machinery" responsible for tissue maintenance. It was these cells, known as satellite or progenitor cells, that the scientists wanted to mobilize.

First, the Wake Forest Baptist scientists investigated whether muscle progenitor cells could be mobilized into an implanted scaffold, which basically serves as a "home" for the cells to grow and develop. Scaffolds were implanted in the lower leg muscle of rats and retrieved for examination after several weeks.

Lab testing revealed that the scaffolds contained muscle satellite cells as well as stem cells that could be differentiated into muscle cells in the lab. In addition, the scaffold had developed a network of blood vessels, with mature vessels forming four weeks after implantation.

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Research in rodents suggests potential for 'in body' muscle regeneration

The medical community has long thought the heart muscle had zero regenerative ability; once it was damaged or otherwise made ineffective, there was no chance of the body making new cells to replace the old ones. That way of thinking is about to change, however, thanks to a new study from Vanderbilt University.

Cardiac stem cells, cells that can create new heart muscle, have been identified inside arteries. The discovery came about as scientists closely examined endothelial cells that line the inner surface of blood vessels. These cells have been known to generate other cells types during mammalian development.

SEE ALSO: Heart attack signs and symptoms in women

People thought that the same heart you had as a young child, you had as an old man or woman as well, said researcher Antonis Hatzopoulos in a press release. Our study suggests that coronary artery disease could lead to heart failure not only by blocking the arteries and causing heart attacks, but also by affecting the way the heart is maintained and regenerated.

What Hatzopoulos and his team suggest is that while the body is healthy and the heart is functioning at a normal level, the cardiac stem cells in the arteries maintain the heart muscle, regenerating cells as needed. When illness like coronary artery disease or a medical emergency like a heart attack occur, these stem cells stop making healthy muscle tissue and start making scar tissue instead. This switch can further complicate heart failure by creating another way arteries become blocked.

It looks like the same endothelial system generates myocytes (muscle cells) during homeostasis and then switches to generate scar tissue after a myocardial infarction. After injury, regeneration turns to fibrosis, said Hatzopoulos. If we can understand the molecular mechanisms that regulate the fate switch that happens after injury, perhaps we can use some sort of chemical or drug to restore regeneration and make muscle instead of scar. We think there is an opportunity here to improve the way we treat people who come into the clinic after myocardial infarction (heart attack).

SEE ALSO: Heart attacks increase health issues in partners, spouses

The key in future research will be to uncover why the cardiac stem cells in the arteries switch from making healthy cells to making scar tissue cells. By learning to control this switch, experts may be able to one day encourage the body to make new heart tissue after a heart attack or to combat age and other disease issues.

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Cardiac stem cells have been discovered | Voxxi

Prof Noel Caplice, director of the Centre for Research in Vascular Biology at University College Cork, displays his stent mesh. Photograph: Michael MacSweeney/Provision

As Prof Noel Caplice describes it, a revolutionary new system that avoids putting patients through heart bypass operations was literally a back-of- the-garage effort.

A cardiologist in Cork, he came up with the treatment when working as a cardiologist at the Mayo Clinic seven years ago. During this time, Caplice and an engineer friend worked on prototype meshes and attaching these to stents.

The treatment introduces cells that encourage the body to make new blood vessels that grow past the blockage, actually reversing the disease in as little as three or four weeks.

The treatment may also offer hope for patients suffering from other cardiovascular disorders such as peripheral artery disease, a common risk in diabetes. And, because it uses the patients own cells, there is no question of rejection, says Caplice, director of University College Corks Centre for Research in Vascular Biology.

This would represent a major step forward in the treatment of coronary artery disease, he adds. Instead of open-heart surgery and stitching in arteries to bypass a blockage, it causes the body to grow its own bypass. He is leading the research, which also involves the Mayo Clinic in the US, and the team has published a paper describing the work in the current issue of the journal Biomaterials.

He came up with the idea when working as a cardiologist at the Mayo Clinic seven years ago, he says.

One area we were interested in was patients who were inoperable, patients who were too ill to face open-heart surgery and who had no options. That represents about 20 to 25 per cent of all patients with coronary artery disease.

He was a scientist physician while at the Mayo as he is now, doing research but also working with patients, and he ran his own laboratory. He originally thought of introducing stem cells to encourage blood vessel growth, but when injected they go everywhere, you cant direct them in the body.

Caplice is also a consultant cardiologist at Cork University Hospital.

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Bypassing surgery for new cardiac treatment

Could this experimental treatment reverse damage caused by a heart attack?

The heart muscle relies on a steady flow of oxygen-rich blood to nourish it and keep it pumping. During a heart attack, that blood flow is interrupted by a blockage in an artery. Without blood, the area of heart fed by the affected artery begins to die and scar tissue forms in the area. Over time, this damage can lead to heart failure, especially when one heart attack comes after another.

Though the heart is a tough organ, the damaged portions become unable to pump blood as efficiently as they once could. People who have had a heart attack therefore may face a lifetime of maintenance therapymedications and other treatments aimed at preventing another heart attack and helping the heart work more efficiently.

A new treatment using stem cellswhich have the potential to grow into a variety of heart cell typescould potentially repair and regenerate damaged heart tissue. In a study published last February in The Lancet, researchers treated 17 heart attack patients with an infusion of stem cells taken from their own hearts. A year after the procedure, the amount of scar tissue had shrunk by about 50%.

These results sound dramatic, but are they an indication that we're getting close to perfecting this therapy? "This is a field where, depending on which investigator you ask, you can get incredibly different answers," says Dr. Richard Lee, professor of medicine at Harvard Medical School and a leading expert on stem cell therapy.

"The field is young. Some studies show only modest or no improvement in heart function, but others have shown dramatically improved function," he says. "We're waiting to see if other doctors can also achieve really good results in other patients."

Studies are producing such varied outcomes in part because researchers are taking different approaches to harvesting and using stem cells. Some stem cells are taken from the bone marrow of donors, others from the patient's own heart. It's not clear which approach is the most promising.

Several different types of approaches are being used to repair damaged heart muscle with stem cells. The stem cells, which are often taken from bone marrow, may be inserted into the heart using a catheter. Once in place, stem cells help regenerate damaged heart tissue.

Like any other therapy, injecting stem cells into the heart can fail or cause side effects. If the stem cells are taken from an unrelated donor, the body's immune system may reject them. And if the injected cells can't communicate with the heart's finely tuned electrical system, they may produce dangerous heart rhythms (arrhythmias). So far, side effects haven't been a major issue, though, and that has encouraged investigators to push onward.

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Repairing the heart with stem cells - Harvard Health ...

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries -- a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

The finding that coronary arteries house a cardiac stem cell "niche" has interesting implications, Hatzopoulos said. Coronary artery disease -- the No. 1 killer in the United States -- would impact this niche.

"Our study suggests that coronary artery disease could lead to heart failure not only by blocking the arteries and causing heart attacks, but also by affecting the way the heart is maintained and regenerated," he said.

The current research follows a previous study in which Hatzopoulos and colleagues demonstrated that after a heart attack, endothelial cells give rise to the fibroblasts that generate scar tissue.

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Coronary arteries hold heart-regenerating cells

ROCHESTER, Minn. (KTTC) -- Medical officials are talking about a breakthrough clinical trial that could help the heart repair itself.

On Tuesday afternoon, Mayo Clinic and Cardio3 BioSciences officials outlined an FDA-approved clinical trial to be carried out in the United States. A similar trial has already been underway in Europe.

Cardio3 CEO Christian Homsy said stem cells are a major part of this heart-healing process. "What we do is take cells from a patient and we reprogram those cells to become cardiac reparative cells. Those cells have the ability to come and repair the heart." Those stem cells would come from the bone marrow of patients who suffer from heart failure.

This treatment is the result of a Mayo Clinic discovery. In Mayo's breakthrough process, stem cells that are harvested from a cardiac patient's bone marrow undergo a guided treatment designed to improve heart health in people suffering from heart failure.

Cardio3 officials said a manufacturing facility will be the first thing that is needed for this clinical trial, and the rest of the details like staffing will follow.

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Trial to use stem cells to repair heart

PUBLIC RELEASE DATE:

20-Aug-2014

Contact: Craig Boerner craig.boerner@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

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Vanderbilt researchers find that coronary arteries hold heart-regenerating cells

4 hours ago Cells grown on hydrogels of the same stiffness all display fat cell markers and deform the underlying matrix material the same way. Credit: Adam Engler, UC San Diego Jacobs School of Engineering

Bioengineers at the University of California, San Diego have proven that when it comes to guiding stem cells into a specific cell type, the stiffness of the extracellular matrix used to culture them really does matter. When placed in a dish of a very stiff material, or hydrogel, most stem cells become bone-like cells. By comparison, soft materials tend to steer stem cells into soft tissues such as neurons and fat cells. The research team, led by bioengineering professor Adam Engler, also found that a protein binding the stem cell to the hydrogel is not a factor in the differentiation of the stem cell as previously suggested. The protein layer is merely an adhesive, the team reported Aug. 10 in the advance online edition of the journal Nature Materials.

Their findings affirm Engler's prior work on the relationship between matrix stiffness and stem cell differentiations.

"What's remarkable is that you can see that the cells have made the first decisions to become bone cells, with just this one cue. That's why this is important for tissue engineering," said Engler, a professor at the UC San Diego Jacobs School of Engineering.

Engler's team, which includes bioengineering graduate student researchers Ludovic Vincent and Jessica Wen, found that the stem cell differentiation is a response to the mechanical deformation of the hydrogel from the force exerted by the cell. In a series of experiments, the team found that this happens whether the protein tethering the cell to the matrix is tight, loose or nonexistent. To illustrate the concept, Vincent described the pores in the matrix as holes in a sponge covered with ropes of protein fibers. Imagine that a rope is draped over a number of these holes, tethered loosely with only a few anchors or tightly with many anchors. Across multiple samples using a stiff matrix, while varying the degree of tethering, the researchers found no difference in the rate at which stem cells showed signs of turning into bone-like cells. The team also found that the size of the pores in the matrix also had no effect on the differentiation of the stem cells as long as the stiffness of the hydrogel remained the same.

"We made the stiffness the same and changed how the protein is presented to the cells (by varying the size of the pores and tethering) and ask whether or not the cells change their behavior," Vincent said. "Do they respond only to the stiffness? Neither the tethering nor the pore size changed the cells."

"We're only giving them one cue out of dozens that are important in stem cell differentiation," said Engler. "That doesn't mean the other cues are irrelevant; they may still push the cells into a specific cell type. We have just ruled out porosity and tethering, and further emphasized stiffness in this process."

Explore further: Researchers find stem cells remember prior substrates

More information: Interplay of matrix stiffness and protein tethering in stem cell differentiation, Nature Materials, DOI: 10.1038/nmat4051

(Phys.org) A team of researchers working at the University of Colorado has found that human stem cells appear to remember the physical nature of the structure they were grown on, after being moved to a ...

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Matrix stiffness is an essential tool in stem cell differentiation, bioengineers report

Yoshiki Sasai, who was embroiled in a stem-cell scandal, committed suicide He was found with a rope around his neck at science institute Riken in Japan Mr Sasai, 52, was deputy chief of Riken's Center for Developmental Biology He co-authored stem-cell research papers with falsified contents

By Ted Thornhill

Published: 06:20 EST, 5 August 2014 | Updated: 13:25 EST, 5 August 2014

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A senior Japanese scientist embroiled in a stem-cell research scandal died on Tuesday in an apparent suicide, police said.

Yoshiki Sasai, who supervised and co-authored stem-cell research papers that had to be retracted due to falsified contents, was found suffering from cardiac arrest at the government-affiliated science institute Riken in Kobe, in western Japan, according to Hyogo prefectural police.

Sasai, 52, was deputy chief of Riken's Center for Developmental Biology.

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Japanese scientist stem-cell scientist Yoshiki Sasai commits suicide

A Japanese scientist who was among a team of researchers accused of falsifying the results of two stem cell studies committed suicide Tuesday at a government science institute in western Japan. Yoshiki Sasai, deputy director of the Riken Center for Developmental Biology, was found by a security guard at the Kobe facility with a rope around his neck, the Associated Press reports. Authorities said he had suffered from cardiac arrest and was pronounced dead two hours later.

Sasai, 52, was considered an expert in embryonic stem cell research and co-authored two research papers published in January in the journal Nature that detailed a seemingly groundbreaking method of harvesting stem cells to grow new human tissue. Sasai and lead author Haruko Obokata reported having successfully altered ordinary mouse cells into versatile stem cells by immersing them in a mildly acidic solution. The resulting cells were named stimulus-triggered acquisition of pluripotency (STAP) cells.

The studies were initially praised as being on the cutting edge of stem cell treatment, but were quickly disputed when other scientists could not replicate the experimental procedure. The papers were retracted six months later after the journal found they contained erroneous data, among other flaws.

Scientists at RIKEN Center for Developmental Biology in Kobe are deeply concerned about the allegations regarding the recently reported STAP cells, the center said in a statement released in March. We wish to express our strong commitment to maintaining the highest level of scientific integrity to the public and the scientific community. We are fully aware that trust from the society is crucial for research activities carried out in RIKEN.

The scandal apparently affected Sasais health. Following the initial revelation that the research he was involved in may have been flubbed, he was hospitalized in March for stress, according to Riken spokesman Satoru Kagaya, who told reporters during a televised news conference on Tuesday that Sasai "seemed completely exhausted" when they talked over the phone in May.

Several suicide notes were found on Sasais secretarys desk, according to the Wall Street Journal. The content of the notes has not been made public, but officials said two of the notes were addressed to Riken officials, one of whom was Obokata.

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Yoshiki Sasai Suicide: Japanese Stem Cell Scientist Found Dead In Kobe Facility

Abstract

Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms, though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation. There are still several major hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Finally, stem cell therapy needs to be safe, reproducible, and affordable. In this review, we will give an introduction to the principles of stem cell based cardiac repair.

Keywords: Stem cell, Regeneration, Heart, Cardiomyocytes

Repairing the injured body with its own tissue as a substrate has captured human fascination for a long time. In Greek mythology, the Lernaean Hydra was a serpent-like creature with multiple heads that regenerated each time they were cut off and Prometheus, a titan punished by Zeus for stealing fire, had a liver that was able to regenerate each night after it was eaten by an eagle. In 1740, Abraham Tembley discovered that microscopic, freshwater animals had the ability to regenerate their head after amputation, later followed by others who discovered that amphibians have the ability to regenerate their tails, limbs, jaws, and eyes.[1],[2] It took scientists until 1933 before they discovered that some human organs, such as the liver, also have the ability to regenerate.[3]

Regenerative therapies are of major interest in cardiovascular medicine. Most cardiovascular diseases, including ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes and in other diseases, such as sick sinus syndrome, specific cardiac cell properties are missing. Unlike the Lernaean Hydra or the human liver, the heart does not have the ability to regenerate itself spontaneously once damaged. Cardiomyocytes are terminally differentiated and have a limited proliferative capacity. Lost cardiomyocytes are replaced by fibroblasts and connective tissue with the remaining cardiomyocytes becoming hypertrophic, which may eventually lead to heart failure. On the contrary, stem cells proliferate indefinitely and can be directed to differentiate into specialized cell types such as cardiomyocytes. The goal of stem cell-based regenerative medicine in cardiovascular disease, therefore, is to create healthy, functional cardiac cells that are able to integrate in the injured heart and restore its function.

In the past decades, several stem cell types have been discovered. These stem cells can be subdivided based on their differentiation capacity. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are able to differentiate into all three embryonic germ layers, whereas multipotent stem cells can differentiate into a number of closely related cell types of a single embryonic germ layer. Cardiomyocytes were derived from several stem cell sources (). Other types of stem cells do not differentiate into cardiomyocytes themselves, but support cardiac repair by different mechanisms (). In this review, we will refer to all stem cell-derived cardiomyocytes and differentiated cell types enriched for cardiomyocytes as stem cell-derived cardiomyocytes (SCD-CMs), while we will refer to non-cardiomyocyte derivatives (such as vascular cells) as stem cell-derived cardiac support cells (SCD-CSCs).

Summary of stem cells used for cardiac repair.

Characteristics of stem cells studied for cardiac regeneration potential.

In this review, we will give an introduction to the principles of stem cell-based cardiac repair. Our aim is to give a concise up-to date overview of the therapeutic possibilities of stem cells for cardiac injury. First, we describe general requirements for stem cell therapy. After that, we will discuss in more detail the different stem cell sources and their therapeutic effects, since these vary for each cell type.

In order to be suitable for cardiac repair, stem cell-derived cardiac cells should resemble the original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Ideally there would also be beneficial effects on the host myocardium, for example, by stimulating proliferation or differentiation of local progenitors, neovascularization or by inhibiting apoptosis. The minimum requirement for the donor cells is to have no adverse effects. Finally, stem cell therapy needs to be safe, reproducible, and affordable. Each of these requirements will be discussed separately. ()

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Stem cells for cardiac repair: an introduction