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.

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Stem Cell Research at Johns Hopkins Medicine: Repairing Heart Damage

BACKGROUND:

SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.

A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 1.6% to 35.1 2.4% [P=0.004, n=8] and 41.2 4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 3.5 g [-30.2%] at 12 months [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 3.9 g [-58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 11.0 g at 12 months [P=0.035]).

Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration.

This study is registered with clinicaltrials.gov, trial number NCT00474461.

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Administration of cardiac stem cells in patients with ischemic ...

Stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials, but a key for better clinical outcomes is to determine the optimal stem cell type best suited for cardiac regeneration, Steven B. Houser, from Temple University (Pennsylvania, USA), and colleagues report that cortical bone-derived stem cells (CBSCs) may be superior to cardiac stem cells, for the regeneration of heart tissue. The researchers collected CBSCs from mouse tibias. The particular mice used had been engineered with green fluorescent protein (GFP), which meant that the CBSCs carried a green marker to allow for their later identification. The cells were then expanded in petri dishes in the laboratory before being injected directly into the hearts of non-GFP mice that had suffered heart attacks. Some mice received cardiac stem cells instead of CBSCs. In the following weeks, as the team monitored the progress of the mice, they found that the youthfulness of the CBSCs had prevailed. The cells had triggered the growth of new blood vessels in the injured tissue, and six weeks after injection, they had differentiated, or matured, into heart muscle cells. While generally smaller than native heart cells, the new cells had the same functional capabilities, and overall they had improved survival and heart function. The study authors submit that: CBSCs improve survival, cardiac function, and attenuate remodeling through the following 2 mechanisms: (1) secretion of proangiogenic factors that stimulate endogenous neovascularization, and (2) differentiation into functional adult myocytes and vascular cells.

Duran JM, Makarewich CA, Sharp TE, Starosta T, Zhu F, Hoffman NE, Houser SR, et al. Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms. Circ Res. 2013 Aug 16;113(5):539-52.

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Bone-Derived Stem Cells for Heart Repair | Worldhealth.net Anti ...

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.

Reviewed: 04/13

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

Medical investigators are embarking on a study that involves infusing 10 million stem cells directly into a coronary artery of heart attack patients in an effort to regenerate tissue that otherwise would be forever damaged.

Regeneration has been an ongoing theme in science fiction and a goal of real-life scientists.

Dr. Luis Gruberg, of the Stony Brook Heart Institute, and Dr. Allen Jeremias, director of the intensive care unit, led a team late last month in a novel case, which they describe as a clinical trial designed to harvest, and then inject, a patient's own stem cells into the blocked artery responsible for the attack.

"This is a post-heart attack procedure and it is for patients who have had a large heart attack," said Gruberg, director of interventional cardiology research.

In patients whose attacks are severe, vast portions of the heart are irreparably damaged, resulting in cardiac tissue that no longer performs efficiently.

Every year about 715,000 Americans have a heart attack. Of those, 525,000 are a first heart attack and 190,000 are repeat episodes. Every 44 seconds someone in the United States dies of a heart attack, according to federal data.

If stem cells can aid in the remodeling of the heart, regenerating healthy tissue, then medicine can offer patients a new lease on life, the doctors said.

Arriving at a point when such a treatment can be offered, Gruberg added, requires research. The gold standard of clinical study in Western medicine is the placebo-controlled randomized clinical trial, which means some of the Stony Brook heart patients will receive a stem cell transplant, others, a placebo.

Doctors began their study, part of a larger national investigation, abruptly late last month because they had been awaiting the perfect patient.

That person, a 66-year-old man who had been visiting Long Island from the Midwest, arrived at Stony Brook University Hospital as a transfer from Southampton Hospital.

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Study to infuse stem cells into coronary artery to regenerate ...

This article is about the medical therapy. For the cell type, see Stem cell.

Stem cell therapy is an intervention strategy that introduces new adult stem cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering.[1] The ability of stem cells to self-renew and give rise to subsequent generations with variable degrees of differentiation capacities,[2] offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.

A number of stem cell therapies exist, but most are at experimental stages, costly or controversial,[3] with the notable exception of bone-marrow transplantation.[citation needed] Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, Parkinson's disease, Huntington's disease, Celiac disease, cardiac failure, muscle damage and neurological disorders, and many others.[4] Nevertheless, before stem cell therapeutics can be applied in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation as well as the mechanisms of stem cell interaction with the diseased/injured microenvironment.[4]

For over 30 years, bone-marrow, and more recently, umbilical-cord blood stem cells, have been used to treat cancer patients with conditions such as leukemia and lymphoma.[5][6] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment.

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). In pregnancy and after injury, this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formed.[citation needed] Although the reparative process appears to initiate following trauma to the brain, substantial recovery is rarely observed in adults, suggesting a lack of robustness.[7]

Stem cells may also be used to treat brain degeneration, such as in Parkinson's and Alzheimer's disease.[8][9]

Pharmacological activation of an endogenous population of neural stem cells / neural precursor cells by soluble factors has been reported to induce powerful neuroprotection and behavioral recovery in adult rat models of neurological disorder through a signal transduction pathway involving the phosphorylation of STAT3 on the serine residue and subsequent Hes3 expression increase (STAT3-Ser/Hes3 Signaling Axis).[10][11][12]

Stem cell technology gives hope of effective treatment for a variety of malignant and non-malignant diseases through the rapid developing field that combines the efforts of cell biologists, geneticists and clinicians. Stem cells are defined as totipotent progenitor cells capable of self-renewal and multi-lineage differentiation. Stem cells survive well and show steady division in culture which then causes them the ideal targets for vitro manipulation. Research into solid tissue stem cells has not made the same progress as haematopoietic stem cells because of the difficulty of reproducing the necessary and precise 3D arrangements and tight cell-cell and cell-extracellular matrix interactions that exist in solid organs. Yet, the ability of tissue stem cells to assimilate into the tissue cytoarchitecture under the control of the host microenvironment and developmental cues, makes them ideal for cell replacement therapy. [3] [13]

The development of gene therapy strategies for treatment of intra-cranial tumours offers much promise, and has shown to be successful in the treatment of some dogs;[14] although research in this area is still at an early stage. Using conventional techniques, brain cancer is difficult to treat because it spreads so rapidly. Researchers at the Harvard Medical School transplanted human neural stem cells into the brain of rodents that received intracranial tumours. Within days, the cells migrated into the cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce the tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic.[15]

Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cells. Accordingly, current cancer treatments are designed to kill cancer cells. However, conventional chemotherapy treatments cannot discriminate between cancerous cells and others. Stem cell therapies may serve as potential treatments for cancer.[16] Research on treating lymphoma using adult stem cells is underway and has had human trials. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.

Read more here:
Stem cell therapy - Wikipedia, the free encyclopedia

Results from a ground-breaking Cedars-Sinai Heart Institute clinical trial show that an infusion of cardiac stem cells helps damaged hearts regrow healthy muscle.

The first-in-man clinical trial, based on technologies and discoveries made by Eduardo Marbn, MD, PhD, and led by Raj Makkar, MD, explored the safety of harvesting, growing and giving patients their own cardiac stem cells to repair heart tissue injured by heart attack.

The studys findings, published in The Lancet, show that heart attack patients who received stem cell treatment demonstrated a significant reduction in the size of the scar left on the heart muscle; this is a pioneering stem cell result, says Marban, who notes the study shows actual regeneration of tissues. With support from the California Institute for Regenerative Medicine, the Heart Institute team is now planning future clinical trials to treat advanced heart disease patients with stem cells.

The process to grow cardiac-derived stem cells involved in the study was developed earlier by Marbn when he was on the faculty of Johns Hopkins University. The university has filed for a patent on that intellectual property, and has licensed it to a company in which Marbn has a financial interest. No funds from that company were used to support the clinical study. All funding was derived from the National Institutes of Health and Cedars-Sinai Medical Center.

Since the Cedars-Sinai team completed the worlds first cardiac stem cell infusion in 2009, additional insights have emerged from this and related work, including the discovery in animals that iron-infused cardiac stem cells can be guided with a magnet to damaged areas of the heart, dramatically increasing their retention and healing potential.

Another finding to emerge from Marbns cardiac stem cell lab may have implications for many peoples health: Stem cells exposed to high doses of supplemental antioxidants can develop genetic abnormalities that predispose them to cancer formation.

Click here to watch a CBS Evening News story about the clinical trials results.

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Cardiac Stem Cell Research - Cedars-Sinai

Heart attacks and congestive heart failure remain among the Nation's most prominent health challenges despite many breakthroughs in cardiovascular medicine. In fact, despite successful approaches to prevent or limit cardiovascular disease, the restoration of function to the damaged heart remains a formidable challenge. Recent research is providing early evidence that adult and embryonic stem cells may be able to replace damaged heart muscle cells and establish new blood vessels to supply them. Discussed here are some of the recent discoveries that feature stem cell replacement and muscle regeneration strategies for repairing the damaged heart.

For those suffering from common, but deadly, heart diseases, stem cell biology represents a new medical frontier. Researchers are working toward using stem cells to replace damaged heart cells and literally restore cardiac function.

Today in the United States, congestive heart failurethe ineffective pumping of the heart caused by the loss or dysfunction of heart muscle cellsafflicts 4.8 million people, with 400,000 new cases each year. One of the major contributors to the development of this condition is a heart attack, known medically as a myocardial infarction, which occurs in nearly 1.1 million Americans each year. It is easy to recognize that impairments of the heart and circulatory system represent a major cause of death and disability in the United States [5].

What leads to these devastating effects? The destruction of heart muscle cells, known as cardiomyocytes, can be the result of hypertension, chronic insufficiency in the blood supply to the heart muscle caused by coronary artery disease, or a heart attack, the sudden closing of a blood vessel supplying oxygen to the heart. Despite advances in surgical procedures, mechanical assistance devices, drug therapy, and organ transplantation, more than half of patients with congestive heart failure die within five years of initial diagnosis. Research has shown that therapies such as clot-busting medications can reestablish blood flow to the damaged regions of the heart and limit the death of cardiomyocytes. Researchers are now exploring ways to save additional lives by using replacement cells for dead or impaired cells so that the weakened heart muscle can regain its pumping power.

How might stem cells play a part in repairing the heart? To answer this question, researchers are building their knowledge base about how stem cells are directed to become specialized cells. One important type of cell that can be developed is the cardiomyocyte, the heart muscle cell that contracts to eject the blood out of the heart's main pumping chamber (the ventricle). Two other cell types are important to a properly functioning heart are the vascular endothelial cell, which forms the inner lining of new blood vessels, and the smooth muscle cell, which forms the wall of blood vessels. The heart has a large demand for blood flow, and these specialized cells are important for developing a new network of arteries to bring nutrients and oxygen to the cardiomyocytes after a heart has been damaged. The potential capability of both embryonic and adult stem cells to develop into these cells types in the damaged heart is now being explored as part of a strategy to restore heart function to people who have had heart attacks or have congestive heart failure. It is important that work with stem cells is not confused with recent reports that human cardiac myocytes may undergo cell division after myocardial infarction [1]. This work suggests that injured heart cells can shift from a quiescent state into active cell division. This is not different from the ability of a host of other cells in the body that begin to divide after injury. There is still no evidence that there are true stem cells in the heart which can proliferate and differentiate.

Researchers now know that under highly specific growth conditions in laboratory culture dishes, stem cells can be coaxed into developing as new cardiomyocytes and vascular endothelial cells. Scientists are interested in exploiting this ability to provide replacement tissue for the damaged heart. This approach has immense advantages over heart transplant, particularly in light of the paucity of donor hearts available to meet current transplantation needs.

What is the evidence that such an approach to restoring cardiac function might work? In the research laboratory, investigators often use a mouse or rat model of a heart attack to study new therapies (see Figure 9.1. Rodent Model of Myocardial Infarction). To create a heart attack in a mouse or rat, a ligature is placed around a major blood vessel serving the heart muscle, thereby depriving the cardiomyocytes of their oxygen and nutrient supplies. During the past year, researchers using such models have made several key discoveries that kindled interest in the application of adult stem cells to heart muscle repair in animal models of heart disease.

Figure 9.1. Rodent Model of Myocardial Infarction.

( 2001 Terese Winslow, Lydia Kibiuk)

Recently, Orlic and colleagues [9] reported on an experimental application of hematopoietic stem cells for the regeneration of the tissues in the heart. In this study, a heart attack was induced in mice by tying off a major blood vessel, the left main coronary artery. Through the identification of unique cellular surface markers, the investigators then isolated a select group of adult primitive bone marrow cells with a high capacity to develop into cells of multiple types. When injected into the damaged wall of the ventricle, these cells led to the formation of new cardiomyocytes, vascular endothelium, and smooth muscle cells, thus generating de novo myocardium, including coronary arteries, arterioles, and capillaries. The newly formed myocardium occupied 68 percent of the damaged portion of the ventricle nine days after the bone marrow cells were transplanted, in effect replacing the dead myocardium with living, functioning tissue. The researchers found that mice that received the transplanted cells survived in greater numbers than mice with heart attacks that did not receive the mouse stem cells. Follow-up experiments are now being conducted to extend the posttransplantation analysis time to determine the longer-range effects of such therapy [8]. The partial repair of the damaged heart muscle suggests that the transplanted mouse hematopoietic stem cells responded to signals in the environment near the injured myocardium. The cells migrated to the damaged region of the ventricle, where they multiplied and became "specialized" cells that appeared to be cardiomyocytes.

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9. Can Stem Cells Repair a Damaged Heart? [Stem Cell Information]

Newswise LOS ANGELES May 30, 2013 Newport Beach-based nonprofit Coalition Duchenne has awarded a $150,000 grant to a Cedars-Sinai Heart Institute team investigating whether an experimental cardiac stem cell treatment could be used to treat Duchenne muscular dystrophy patients who have developed heart disease.

Coalition Duchenne is led by Catherine Jayasuriya, a mother whose 20-year-old son, Dusty Brandom, has cardiomyopathy associated with Duchenne muscular dystrophy. She was inspired to underwrite cardiac stem cell research at Cedars-Sinai after reading about a successful clinical trial led by Eduardo Marbn, MD, PhD, director of the Cedars-Sinai Heart Institute and the Mark S. Siegel Family Professor.

The experimental stem cell therapy, developed by Marbn, is the only treatment shown in clinical trials to regenerate healthy heart muscle. In the clinical trial, patients underwent biopsies during which doctors removed a piece of heart muscle about the size of half a raisin. The heart tissue was then used to grow specialized heart stem cells, which then were injected back into the patients heart. Results published in The Lancet showed that patients experienced an average 50 percent reduction in muscle damaged by heart attack.

I immediately sensed the potential for applying this rapidly evolving treatment to Duchenne, said Jayasuriya. I made it my personal quest to help get this kind of therapy for Duchenne patients.

Jayasuriyas commitment was further cemented when she discovered that Ron Victor, MD, associate director of the Cedars-Sinai Heart Institute, has been working with Duchenne patients as part of his investigation of the cardiac benefits of sildenafil (Viagra) and tadalafil (Cialis).

We know that boys with Duchenne are born with a small scar in the base of their heart, said Victor, the Burns and Allen Chair in Cardiology Research at the Cedars-Sinai Heart Institute. The damage to hearts in boys with Duchenne increases over time. If we can use stem cells to slow or stop heart damage, it could help stall progression of the disease.

The first step in the study is to examine the effect of injecting cardiac stem cells into the hearts of mice with Duchenne. If the data is positive, the experimental treatment could be rapidly approved for use in humans with Duchenne because of cardiac stem cell treatments have been approved for other patient populations, including those with advanced heart disease.

Each year, 20,000 boys are born with Duchenne, Jayasuriya said, who founded Coalition Duchenne in 2010 to raise global awareness for Duchenne muscular dystrophy, fund research and find a cure for Duchenne. Many do not live into their 20s and we lose many to cardiac issues. We need to focus on changing the course of the disease. We hope that working with cardiac stem cells is one way we will eventually change that outcome.

Duchenne muscular dystrophy is a progressive muscle-wasting disease and the most common fatal disease that affects children. Duchenne occurs in one in 3,500 male births, across all races, cultures and countries. Duchenne is caused by a defect in the gene that produces the protein dystrophin, which helps connect the muscle fiber to the cell membranes. Without dystrophin, muscle cells become unstable, are weakened and lose their functionality. Life expectancy of boys and young men with Duchenne ranges from the mid-teens to the mid-20s. Their minds are unaffected.

The Cedars-Sinai Heart Institute is internationally recognized for outstanding heart care built on decades of innovation and leading-edge research. From cardiac imaging and advanced diagnostics to surgical repair of complex heart problems to the training of the heart specialists of tomorrow and research that is deepening medical knowledge and practice, the Cedars-Sinai Heart Institute is known around the world for excellence and innovations.

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Grant Funds Research Into Cardiac Stem Cells as Treatment for Heart Disease Related to Duchenne Muscular Dystrophy

R. Bolli - Interim Results of the SCIPIO Trial Up to 2 Years After Therapy
R. Bolli - Effect of Cardiac Stem Cells in Patients with Ischemic Cardiomyopathy: Interim Results of the SCIPIO Trial Up to 2 Years After Therapy SCIPIO: (Cardiac) Stem Cell Infusion in Patients with Ischemic cardiomyopathy Annual Session of the American Heart Association November 5, 2012, Los AngelesFrom:CardioletterViews:3 0ratingsTime:09:07More inScience Technology

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R. Bolli - Interim Results of the SCIPIO Trial Up to 2 Years After Therapy - Video

By E.J. Mundell HealthDay Reporter

TUESDAY, Nov. 6 (HealthDay News) -- Updated two-year results from a small trial using cardiac stem cells to repair damaged hearts suggest the treatment's healing effect persists.

Patients with heart failure caused by prior heart attacks who got the treatment continue to see reductions in cardiac scar tissue, improvements in the heart's pumping ability and even a boost in their quality of life, researchers said.

These improvements seem to be continuing as time goes on, suggesting that stem cell therapy's healing power hasn't diminished.

"Now we need to perform larger and randomized, blinded studies ... to confirm this data," said study lead author Dr. Roberto Bolli, director of the Institute of Molecular Cardiology at the University of Louisville.

His team presented its results Tuesday at the American Heart Association's annual meeting, in Los Angeles.

According to the AHA, more than 6 million Americans suffer from heart failure, a gradual weakening of the heart often caused by damage from a prior heart attack. Despite its prevalence and lethality, virtually no advance has been made over the past few decades in doctors' ability to treat or reverse heart failure.

That's why the advent of stem cell therapy has encouraged researchers. Stem cells have the ability to turn into myriad living cells, and the hope is that once infused into the heart they can help repair it.

This trial is the first human trial to test this theory using the patient's own cardiac stem cells. The cells used in the trial were harvested from 33 heart failure patients who were undergoing bypass surgery. The cells were then coaxed to multiply into the millions in the lab and then transplanted back into 20 of the patients. The remaining 13 patients did not receive a stem cell infusion and are the "control" group for comparison purposes.

Results gathered one year after treatment showed improvements for the treated patients, but experts questioned whether those gains would fade over time.

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Two Years On, Stem Cells Still Healing Damaged Hearts

Study Highlights:

LOS ANGELES, Nov. 6, 2012 (GLOBE NEWSWIRE) -- Cardiac stem cells may one day be an effective treatment for heart failure caused by muscle scarring after a heart attack, according to late-breaking clinical trial results presented at the American Heart Association's Scientific Sessions 2012.

In the Effect of Cardiac Stem Cells In Patients with Ischemic CardiOmyopathy (SCIPIO) trial, heart function and quality of life improved in 20 people treated with their own cardiac stem cells (CSCs).

"This is exciting," said Roberto Bolli, M.D., lead author of the trial, chief of Cardiovascular Medicine and director of the Institute of Molecular Cardiology at the University of Louisville in Kentucky. "The effect of these cells has continued for up to two years, and has gotten stronger. There was also a major reduction in heart scarring."

In 33 patients with heart failure who had undergone coronary artery bypass surgery, researchers removed a tiny piece of heart tissue and isolated heart stem cells called c-kit CSCs. Researchers then grew additional cells to infuse into 20 volunteers assigned to treatment.

Among outcomes found two years after treatment:

"We have not seen any deaths among the patients, or any adverse effects that can be ascribed to the stem cells," Bolli said.

About 6.6 million Americans suffer from heart failure, according to the American Heart Association. Life expectancy is about five years after diagnosis. Ischemic heart attacks cause most of the 57,000 U.S. deaths a year due to heart failure.

Larger, multi-center studies are needed to confirm the findings, Bolli said.

The Jewish Hospital, University of Louisville, and the National Institutes of Health funded the study. Co-authors' names are on the abstract.

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Cardiac Stem Cells May Help Treat Heart Failure

Public release date: 16-Oct-2012 [ | E-mail | Share ]

Contact: Bryan Ghosh bghosh@plos.org 44-122-344-2837 Public Library of Science

Researchers at the University of Helsinki believe they have discovered stem cells that play a decisive role in the growth of new blood vessels. If researchers learn to isolate and efficiently produce these stem cells found in blood vessel walls, the cells could offer new opportunities for developing therapeutics to treat diseases, such as cardiovascular disease and cancer. The study reporting the discovery of these stem cells is published in the open access journal PLOS Biology on October 16.

The growth of new blood vessels, known as neoangiogenesis, occurs during the repair of damaged tissue and organs in adults. However, malignant tumours also grow new blood vessels in order to receive oxygen and nutrients. As such, neoangiogenesis is both beneficial and detrimental to health, depending on the context, requiring therapeutic approaches that can either help to stimulate or prevent it. Therapeutics that aim to prevent the growth of new blood vessels are already in use, but the results are often more modest than predicted.

Adjunct Professor Petri Salvn and his team, from the University of Helsinki, now report that these stem cells can be found among the cellsso-called endothelial cellsthat line the inside of blood vessel walls. He explains, "we succeeded in isolating endothelial cells with a high rate of division in the blood vessel walls of mice. We found these same cells in human blood vessels and blood vessels growing in malignant tumours in humans. These cells are known as vascular endothelial stem cells, abbreviated as VESC. In a cell culture, one such cell is capable of producing tens of millions of new blood vessel wall cells".

From their studies in mice, the team are able to show that the growth of new blood vessels weakens, and the growth of malignant tumours slows, if the amount of these cells is below normal. Conversely, new blood vessels form where these stem cells are implanted.

"The identification and isolation of an entirely new adult stem cell type is a significant discovery in stem cell biology." explains Salvn. "Endothelial stem cells in blood vessels are particularly interesting, because they offer great potential for applications in practical medicine and the treatment of patients."

If an efficient method of vascular endothelial stem cell production could be developed, it could offer new treatment opportunities in situations where damaged tissue or diseases call for new blood vessel growth, or where the constriction or dysfunction of blood vessels deprives tissues of oxygen, for example in cardiac disease. These cells also offer new opportunities for developing therapeutics that seek to prevent new blood vessel growth in malignant tumours.

###

Funding: The work was supported by the Finnish Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish,or preparation of the manuscript.

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Researchers discover new blood vessel-generating cell with therapeutic potential

It has been a crazy week for stem cell research. After the high of a Nobel prize for Japan's Shinya Yamanaka, the pioneer of cellular reprogramming, events took an alarming and surreal turn when a little-known compatriot Hisashi Moriguchi claimed to have already run a clinical trial in which similarly reprogrammed cells were injected into people.

But Moriguchi's claims quickly unravelled. "I have not found a single person to say anything concrete indicating that this has really happened," says Paul Knoepfler, a stem cell researcher at the University of California, Davis, who tracked the unfolding story on his blog.

In a poster presented at a meeting of the New York Stem Cell Foundation, Moriguchi who claimed to work at Harvard Medical School and the University of Tokyo described results from a trial in which cardiac muscle cells were grown from induced pluripotent stem (iPS) cells, and transplanted into six US patients with severe heart failure.

The Yomiuri Shimbun newspaper Japan's biggest splashed the story, based on an interview with Moriguchi, who claimed he had received ethical approval from Harvard Medical School's Institutional Review Board (IRB).

This was surprising, given the safety concerns that surround iPS cells adult cells that have been reprogrammed to an embryonic state. Support for the claim quickly disintegrated: within hours, Harvard released a statement noting that Moriguchi had no current affiliation with the university, nor any ethical approval to run a clinical trial.

Moriguchi's poster describing the clinical trial was taken down after the New York Stem Cell Foundation learned of Harvard's statement but a summary was published on Knoepfler's blog. This suggested an improvement of 41.5 per cent in "ejection fraction" a measure of heart output in patients whose hearts were injected with iPS-derived cells, compared to 4.1 per cent in a placebo group.

That would have been an astonishing claim, says Michael Laflamme at the University of Washington in Seattle, who is working to develop cell therapies for heart attack: "I'm not aware of any clinical trial that reported anything of this magnitude."

Indeed, similar studies involving adult stem cells have typically found improvements of less than 5 per cent (European Journal of Hearth Failure, doi.org/crq5k6).

Moriguchi did not respond to emails from New Scientist. But on Saturday he admitted to reporters that for five of the patients he was actually describing "planned" procedures. Still, Moriguchi maintained that he had transplanted cells into one patient at an unidentified hospital in Boston.

New Scientist's enquiries raise further questions about Moriguchi's work. In papers published earlier this year, he described experiments on freezing human ovarian tissue (Scientific Reports, doi.org/jht), and a remarkable claim to be able to eliminate liver tumour cells using a reprogramming technique (Scientific Reports, doi.org/jhv). Both gave Harvard and University of Tokyo affiliations, and claimed ethical approval from each institution.

Excerpt from:
Claim of first human stem cell trial unravels

Friday, Oct. 12, 2012

Harvard University said neither it nor Massachusetts General Hospital have ever authorized any iPS-related clinical studies by Hisashi Moriguchi, who claims to have achieved the first clinical application using the revolutionary stem cell technology.

"No clinical trials related to Moriguchi's work have been approved by institutional review boards at either Harvard University or Massachusetts General Hospital," a statement issued by Harvard and related institutes said Thursday.

The statement confirmed that Moriguchi "was a visiting fellow at Massachusetts General Hospital from 1999-2000," but added that he "has not been associated with (the institution) or Harvard since that time."

Moriguchi, a researcher at University of Tokyo Hospital, claimed to be a visiting lecturer at Harvard and to have conducted clinical trials at Massachusetts General Hospital with other researchers to transplant artificial cardiac muscle cells developed from iPS cells into six patients with heart disease.

The claim came just after Shinya Yamanaka of Kyoto University and a British scholar were jointly awarded this year's Nobel Prize in physiology or medicine for their research on iPS cells. Yamanaka and John Gurdon were credited with the discovery that mature human cells can be reprogrammed as immature cells capable of developing into all types of body parts.

"Research has been conducted after going through due procedures, such as consultations with a university ethics committee," Moriguchi claimed. "I have been told my method of creating iPS cells is different from the one used by Yamanaka (and Gurdon), but I have been doing it my way and no problems have been identified after transplants."

Moriguchi, who is thought to have asked a heart surgeon to carry out cell transplants, unveiled details about the treatment at a meeting of annual stem-cell research conference at Rockefeller University in New York held Wednesday and Thursday.

But the event's organizer, the nonprofit New York Stem Cell Foundation, subsequently said it "has received information from Harvard University that raises legitimate questions concerning a poster presentation" by Moriguchi, and has withdrawn it from the conference.

Moriguchi graduated from Tokyo Medical and Dental University with a degree in nursing science and does not have a license to practice medicine, according to a professor who taught him as an undergraduate.

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Doubt cast on clinical stem cell tests

Friday, Oct. 12, 2012

NEW YORK A team of researchers has transplanted artificial cardiac muscle cells developed from multipurpose stem cells into six patients in the United States in the world's first clinical application of iPS cells, one of the researchers said Wednesday.

Shinya Yamanaka, who won this year's Nobel Prize in medicine or physiology for his development of iPS cells, declined comment on the transplants, while other experts said details about the medical performance should be carefully evaluated.

The researchers developed the muscle cells from induced pluripotent stem cells produced from the patients' livers and transplanted them to the patients, said Hisashi Moriguchi, a visiting professor at Harvard University.

A 34-year-old American male patient who was the first to receive the transplant in February now has normal heart functions and has been discharged from the hospital, Moriguchi said.

The patient suffered from liver cancer and received a liver transplant in February 2009. He developed ischemic cardiomyopathy this February, prompting the researchers to conduct the heart surgery.

The researchers took cells from the patient's original liver, which was kept after removal for the 2009 transplant, and developed iPS cells by adding protein and other medical agents from which they produced cardiac muscle cells. The muscle cells were placed in 30 locations in the patient's heart.

No rejection or cancer development was found in the heart, and his heart function gradually recovered to normal levels 10 days after the surgery, they said.

"We need to improve the efficacy and safety of such medical treatment . . . and think of ways to reduce economic burden on patients," Moriguchi said.

The researchers used an improved technique to produce iPS cells developed by Yamanaka, the professor from Kyoto University who jointly won this year's Nobel with John Gurdon of Britain. Such cells have the potential to grow into any type of body tissue.

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U.S. marks first iPS clinical applications

Public release date: 10-Sep-2012 [ | E-mail | Share ]

Contact: Bill Seiler bseiler@umm.edu 410-328-8919 University of Maryland Medical Center

Baltimore, MD September 10, 2012 Researchers at the University of Maryland School of Medicine, who are exploring novel ways to treat serious heart problems in children, have conducted the first direct comparison of the regenerative abilities of neonatal and adult-derived human cardiac stem cells. Among their findings: cardiac stem cells (CSCs) from newborns have a three-fold ability to restore heart function to nearly normal levels compared with adult CSCs. Further, in animal models of heart attack, hearts treated with neonatal stem cells pumped stronger than those given adult cells. The study is published in the September 11, 2012, issue of Circulation.

"The surprising finding is that the cells from neonates are extremely regenerative and perform better than adult stem cells," says the study's senor author, Sunjay Kaushal, M.D., Ph.D., associate professor of surgery at the University of Maryland School of Medicine and director, pediatric cardiac surgery at the University of Maryland Medical Center. "We are extremely excited and hopeful that this new cell-based therapy can play an important role in the treatment of children with congenital heart disease, many of whom don't have other options."

Dr. Kaushal envisions cellular therapy as either a stand-alone therapy for children with heart failure or an adjunct to medical and surgical treatments. While surgery can provide structural relief for some patients with congenital heart disease and medicine can boost heart function up to two percent, he says cellular therapy may improve heart function even more dramatically. "We're looking at this type of therapy to improve heart function in children by 10, 12, or 15 percent. This will be a quantum leap in heart function improvement."

Heart failure in children, as in adults, has been on the rise in the past decade and the prognosis for patients hospitalized with heart failure remains poor. In contrast to adults, Dr. Kaushal says heart failure in children is typically the result of a constellation of problems: reduced cardiac blood flow; weakening and enlargement of the heart; and various congenital malformations. Recent research has shown that several types of cardiac stem cells can help the heart repair itself, essentially reversing the theory that a broken heart cannot be mended.

Stem cells are unspecialized cells that can become tissue- or organ-specific cells with a particular function. In a process called differentiation, cardiac stem cells may develop into rhythmically contracting muscle cells, smooth muscle cells or endothelial cells. Stem cells in the heart may also secrete growth factors conducive to forming heart muscle and keeping the muscle from dying.

To conduct the study, researchers obtained a small amount of heart tissue during normal cardiac surgery from 43 neonates and 13 adults. The cells were expanded in a growth medium yielding millions of cells. The researchers developed a consistent way to isolate and grow neonatal stem cells from as little as 20 milligrams of heart tissue. Adult and neonate stem cell activity was observed both in the laboratory and in animal models. In addition, the animal models were compared to controls that were not given the stem cells.

Dr. Kaushal says it is not clear why the neonatal stem cells performed so well. One explanation hinges on sheer numbers: there are many more stem cells in a baby's heart than in the adult heart. Another explanation: neonate-derived cells release more growth factors that trigger blood vessel development and/or preservation than adult cells.

"This research provides an important link in our quest to understand how stem cells function and how they can best be applied to cure disease and correct medical deficiencies," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs, University of Maryland; the John Z. and Akiko K. Bowers Distinguished Professor; and dean, University of Maryland School of Medicine. "Sometimes simple science is the best science. In this case, a basic, comparative study has revealed in stark terms the powerful regenerative qualities of neonatal cardiac stem cells, heretofore unknown."

Excerpt from:
University of Maryland study: Neonatal heart stem cells may help mend kids' broken hearts

Johns Hopkins researchers have discovered that a single protein molecule may hold the key to turning cardiac stem cells into blood vessels or muscle tissue, according to a release from the university. This finding may lead to better ways to treat heart attack patients.

Human heart tissue typically forms scars rather than healing well after an attack. However, stem cells have been shown improve the repair process by turning into the cells that make up healthy heart tissue, including heart muscle and blood vessels. The recent discovery of a master molecule that guides the destiny of these stem cells has the potential to result in even more effective treatments for heart patients, the Johns Hopkins researchers say.

In a study published in the June 5 online edition of journal Science Signaling, the Johns Hopkins team reported that tinkering with a protein molecule called p190RhoGAP shaped the development of cardiac stem cells and prodded them to become the building blocks for either blood vessels or heart muscle. The scientists said that by altering levels of this protein, they were able to affect the future of these stem cells. In biology, finding a central regulator like this is like finding a pot of gold, said Andre Levchenko, a biomedical engineering professor and member of the Johns Hopkins Institute for Cell Engineering, who supervised the research effort.

The lead author of the journal article, Kshitiz, a postdoctoral fellow who uses only his first name, said, Our findings greatly enhance our understanding of stem cell biology and suggest innovative new ways to control the behavior of cardiac stem cells before and after they are transplanted into a patient. This discovery could significantly change the way stem cell therapy is administered in heart patients.

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"Master Molecule" May Help Heart Treatment

COLUMBIA, Md.--(BUSINESS WIRE)--

Osiris Therapeutics, Inc. (OSIR), announced today interim one-year results from its groundbreaking clinical trial evaluating Prochymal (remestemcel-L) for the treatment of patients experiencing first-time acute myocardial infarction. The trial is the largest study of allogeneic or "off-the-shelf" stem cells ever conducted in heart attack patients. A total of 220 patients were given a single infusion of either Prochymal or placebo through a standard intravenous line within seven days of an acute heart attack.

Cardiac MRI assessments were conducted for six months following infarct to evaluate cardiac remodeling. Patients receiving Prochymal had significantly less cardiac hypertrophy, as measured by cardiac MRI, compared to patients receiving placebo (p<0.05). Patients treated with Prochymal also experienced significantly less stress-induced ventricular arrhythmia (p<0.05). Cardiac hypertrophy and ventricular arrhythmia are indicators of pathological remodeling following heart injury and provide insight into the mechanism by which mesenchymal stem cells attenuate heart injury following a myocardial infarction.

The mechanistic data is complemented by clinical data showing treatment with Prochymal resulted in a statistically significant reduction in heart failure. In the study, seven patients who were treated with placebo have progressed to heart failure requiring treatment with intravenous diuretics, compared to none of the Prochymal patients (p=0.01). Furthermore, patients receiving placebo tended to require re-hospitalization for cardiac issues sooner than the patients receiving Prochymal (median 27.5 days vs. 85.5 days).

This study is the largest of its kind and provides key insights into the mechanism of action of mesenchymal stem cells in the setting of acute myocardial infarction, said Lode Debrabandere, Ph.D., Senior Vice President of Therapeutics at Osiris. These important mechanistic observations are consistent with data obtained from our preclinical models and from the first placebo-controlled human trial with Prochymal published in the Journal of the American College of Cardiology. Given the quality of the data and highly encouraging results observed thus far, we are extending the trial's duration to capture a better understanding of the long-term clinical benefits of MSCs."

The trial also demonstrated that treatment with Prochymal was safe. There were no infusional toxicities observed in patients receiving Prochymal. Serious adverse events occurred with equal frequency in both treatment groups (31.8%). To date, there have been 5 deaths in the trial, 2 in the Prochymal group and 3 in the placebo group.

For interventional cardiologists, keeping our myocardial infarction patients from progressing to heart failure is central to our mission, said Mark Vesely, M.D., Principal Investigator on the Study and Assistant Professor of Medicine (Interventional Cardiology) at the University of Maryland School of Medicine. It is remarkable and very encouraging to see significant changes in clinically meaningful parameters this early in the study. We look forward to the additional data that will be gathered as the study progresses, which will help us to better understand both the magnitude and durability of the benefit to treatment.

Prochymal, the worlds first and only stem cell drug approved by an internationally recognized regulatory authority, is used for the treatment of graft vs. host disease (GvHD). GvHD is a devastating complication of bone marrow transplantation that kills up to 80 percent of children affected. Prochymal is now approved in Canada and New Zealand, and is currently available in seven other countries including the United States under an Expanded Access Program (EAP).

About the Trial

This Phase 2, multi-center, randomized, double-blind, placebo-controlled study is evaluating the safety and efficacy of Prochymal (ex-vivo cultured adult human mesenchymal stem cells) intravenous infusion following acute myocardial infarction. A total of 220 patients were randomized (1:1) at 33 centers in the United States and Canada and received a single intravenous infusion of Prochymal or placebo within 7 days following first acute myocardial infarction. In addition to screening and baseline visits prior to the infusion, initially follow-up evaluations were scheduled to be conducted through 2 years. Given the encouraging results observed at the one year time-point, the trial is being extended to include 5 years of follow-up. Both male and female subjects between 21 and 85 years of age were enrolled. Patients had to have a left ventricular ejection fraction (LVEF) between 20% and 45% as determined by quantitative echocardiography or cardiac MRI at least 24 hours after successful reperfusion of the culprit vessel. In addition, troponin levels must have been greater than 4 times the upper limit of normal during the first 72 hours of hospitalization for the MI.

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Prochymal Significantly Reduces Hypertrophy, Arrhythmia and Progression to Heart Failure in Patients Suffering a Heart ...

Editor's Choice Main Category: Muscular Dystrophy / ALS Also Included In: Transplants / Organ Donations Article Date: 29 Jun 2012 - 11:00 PDT

Current ratings for: Stem Cells From Muscular Dystrophy Patients Transplanted Into Mice

A new study published in Science Translational Medicine reveals that researchers have, for the first time, managed to turn fibroblast cells, i.e. common cells within connective tissue, from muscular dystrophy patients into stem cells and subsequently changed these cells into muscle precursor cells. After modifying the muscle precursor cells genetically, the researchers transplanted them into mice.

In future, this new technique could be used in order to treat patients with the rare condition of limb-girdle muscular dystrophy, which primarily affects the shoulders and hips, and maybe other types of muscular dystrophies. The method was initially developed in Milan at the San Raffaele Scientific Institute and was completed at UCL.

Muscular dystrophy is a genetic disorder, which typically affects skeletal muscles. The condition leads to severely impaired mobility and can, in severe cases result in respiratory and cardiac dysfunction. At present, there is no effective treatment for the condition. A number of new potential therapies, including cell therapy, are entering clinical trials.

The scientists of this study concentrated their research on genetically modifying mesoangioblasts, i.e. a self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues, which demonstrated its potential for treating muscular dystrophy in earlier studies.

Given that the muscles of patients with muscular dystrophy are depleted of mesonangioblasts, the researchers were unable to obtain sufficient numbers of these cells from patients with limb-girdle muscular dystrophy, and therefore "reprogrammed" adult cells from these patients into stem cells, which enabled them to prompt them to differentiate into mesoangioblast-like cells.The team then genetically corrected these 'progenitor' cells by using a viral vector, and injected them into mice with muscular dystrophy so that the cells targeted damaged muscle fibers.

In a mice study, the same process demonstrated that dystrophic mice were able to run on a treadmill for longer a longer time than dystrophic mice that did not receive the cells.

Research leader, Dr Francesco Saverio Tedesco, from UCL Cell & Developmental Biology, who led the study, explained:

Professor Giulio Cossu, also an author at UCL, concluded:

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Stem Cells From Muscular Dystrophy Patients Transplanted Into Mice