Stem cell, heart heath study

HOUSTON -

Doctors from the Texas Heart Institute at St. Luke's Episcopal Hospital have found that patients with heart failure may be able to repair the damaged areas of the heart with stem cells from the patient's own bone marrow.

Doctors presented the findings at the American College of Cardiologys 61st Annual Scientific Session Saturday.

The results are from a multi-center clinical study that measured the possible benefits of using a patients own bone marrow cells to repair damaged areas of the heart suffering from severe heart failure, a condition that affects millions of Americans.

The study, which was the largest such investigation to date, found that the hearts of the patients receiving bone marrow derived stem cells showed a small but significant increase in the ability to pump oxygenated blood from the left ventricle, the hearts main pumping chamber, to the body.

The expectation is that the study will pave the way for potential new treatment options and will be important to designing and evaluating future clinical trials.

This is exactly the kind of information we need to move forward with the clinical use of stem cell therapy, said Emerson Perin, MD, PhD, Director of Clinical Research for Cardiovascular Medicine at THI, and one of the studys lead investigators.

The bone-marrow derived stem cells are helpful to the injured heart when they are themselves biologically active, added Dr. James T. Willerson, the studys principal investigator and President and Medical Director of THI.

This study moves us one step closer to being able to help patients with severe heart failure who have no other alternatives.

The study was conducted by the Cardiovascular Cell Therapy Research Network, the national consortium to conduct such research funded by the National Institutes of Healths National Heart, Lung, and Blood Institute.

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Stem cell, heart heath study

Bone Marrow Stem Cell Therapy Trial – Clues, But No Answers

(RTTNews.com) - An important clinical trial, which evaluated the use of autologous bone-marrow-cell therapy in patients with chronic ischemic heart failure, has failed to meet the prespecified end points of improvement in most measures of heart function, according to the results presented at the American College of Cardiology 2012 Scientific Sessions.

The trial dubbed, FOCUS - a phase II study, is the largest study to date to investigate if a patient's own bone marrow cells improved myocardial perfusion, reduced left ventricular end-systolic volume or enhanced maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. The FOCUS trial was undertaken by the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network.

Ninety two patients with chronic ischemic heart disease , having a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography, or SPECT, who were no longer candidates for revascularization, were enrolled in the trial. Sixty one patients in the study were administered bone marrow cells through transendocardial injections while thirty one patients were administered placebo.

An assessment of primary endpoints at 6 months has revealed that there is no statistically significant difference between the treatment group and placebo arm in left ventricular end-systolic volume assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. The secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement, also has not exhibited any difference between the two arms.

However, according to the study authors, exploratory analyses have revealed that left ventricular ejection fraction improved in the treatment group compared with the placebo group by 2.7%.

The authors, led by Emerson Perin, concluded that the findings provide evidence for further studies to determine the relationship between the composition and function of bone marrow product and clinical end points. Understanding these relationships will improve the design and interpretation of future studies of cardiac cell therapy, the authors noted.

The results were published online March 24 in the Journal of the American Medical Association.

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Bone Marrow Stem Cell Therapy Trial - Clues, But No Answers

Stem cell controversy could see new life with regent election shuffle

The departure of three University of Nebraska regents this year and the re-election campaign of a fourth is reviving debate over a controversial issue some believe should be laid to rest.

Two of the three departing regents, Chuck Hassebrook of Lyons and Jim McClurg of Lincoln, opposed a proposal considered by the Board of Regents in November 2009 that would have limited embryonic stem cell research at the University of Nebraska Medical Center to only cell lines approved under former President George W. Bush. Expansion had become a possibility since President Barack Obama relaxed the Bush guidelines.

Hassebrook and McClurg joined two other regents in killing the proposal by voting against the four who supported it. Pro-life activists believe embryonic stem cell research is morally wrong because harvesting the stem cells requires destroying an embryo.

Regent Randy Ferlic of Omaha, who supported the proposal to limit the research, also will leave the Board of Regents after this year. Bob Whitehouse of Papillion, who opposed the measure, is seeking re-election. Ten candidates are seeking the three retiring regents' seats, and candidate, Larry Bradley, is challenging Whitehouse.

Pro-life advocates said they see opportunity in the departure of two of the regents who opposed limiting stem cell research, but they aren't ready to say they'll ask like-minded regents to reintroduce a proposal to limit the research.

"That would be a place we could stand to gain if we had pro-lifers in the race who we're willing to endorse," said Julie Schmit-Albin, executive director of Nebraska Right to Life.

Nebraska Right to Life endorsed McClurg during his regents campaign, and Schmit-Albin said she believed he would have supported limiting embryonic stem cell research. When he voted against the proposal, however, Nebraska Right to Life ended its support of him, she said.

The group has become more careful in choosing candidates to endorse, Schmit-Albin said, sending out surveys to candidates and incumbents seeking re-election before the primary. It has yet to receive responses from those surveys, she said, so Nebraska Right to Life has yet to endorse any candidates this year.

Schmit-Albin said some regents candidates have contacted the group seeking endorsement, but she declined to name them. She said the group wouldn't endorse Whitehouse because he voted against the stem cell proposal in November 2009.

"He already has a record," she said.

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Stem cell controversy could see new life with regent election shuffle

Stem cell therapy could repair some heart damage: Study

Published on Mar 25, 2012

CHICAGO (AFP) - Patients with advanced heart disease who received an experimental stem cell therapy showed slight improvements in blood pumping but no change in most of their symptoms, United States researchers said on Saturday.

Study authors described the trial as the largest to date to examine stem cell therapy as a route to repairing the heart in patients with chronic ischemic heart disease and left ventricular dysfunction.

Previous studies have established that the approach is safe in human patients, but none had examined how well it worked on a variety of heart ailments.

The clinical trial involved 92 patients, with an average age of 63, who were picked at random to get either a placebo or a series of injections of their own stem cells, taken from their bone marrow, into damaged areas of their hearts.

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Stem cell therapy could repair some heart damage: Study

A new shortcut for stem cell programming

ScienceDaily (Mar. 22, 2012) Researchers at the University of Bonn artificially derive brain stem cells directly from the connective tissue of mice.

Scientists at the Life & Brain Research Center at the University of Bonn, Germany, have succeeded in directly generating brain stem cells from the connective tissue cells of mice. These stem cells can reproduce and be converted into various types of brain cells. To date, only reprogramming in brain cells that were already fully developed or which had only a limited ability to divide was possible. The new reprogramming method presented by the Bonn scientists and submitted for publication in July 2011 now enables derivation of brain stem cells that are still immature and able to undergo practically unlimited division to be extracted from conventional body cells. The results have now been published in the current edition of the journal Cell Stem Cell.

The Japanese stem cell researcher Professor Shinya Yamanaka and his team produced stem cells from the connective tissue cells of mice for the first time in 2006; these cells can differentiate into all types of body cells. These induced pluripotent stem cells (iPS cells) develop via reprogramming into a type of embryonic stage. This result made the scientific community sit up and take notice. If as many stem cells as desired can be produced from conventional body cells, this holds great potential for medical developments and drug research. "Now a team of scientists from the University of Bonn has proven a variant for this method in a mouse model," report Dr. Frank Edenhofer and his team at the Institute of Reconstructive Neurobiology (Director: Dr. Oliver Brstle) of the University of Bonn. Also involved were the epileptologists and the Institute of Human Genetics of the University of Bonn, led by Dr. Markus Nthen, who is also a member of the German Center for Neurodegenerative Diseases.

Edenhofer and his co-workers Marc Thier, Philipp Wrsdrfer and Yenal B. Lakes used connective tissue cells from mice as a starting material. Just as Yamanaka did, they initiated the conversion with a combination of four genes. "We however deliberately targeted the production of neural stem cells or brain stem cells, not pluripotent iPS multipurpose cells," says Edenhofer. These cells are known as somatic or adult stem cells, which can develop into the cells typical of the nervous system, neurons, oligodendrocytes and astrocytes.

The gene "Oct4" is the central control factor

The gene "Oct4" is a crucial control factor. "First, it prepares the connective tissue cell for reprogramming, later, however, Oct4 appears to prevent destabilized cells from becoming brain stem cells" reports the Bonn stem cell researcher. While this factor is switched on during reprogramming of iPS cells over a longer period of time, the Bonn researchers activate the factor with special techniques for only a few days. "If this molecular switch is toggled over a limited period of time, the brain stem cells, which we refer to as induced neural stem cells (iNS cells), can be reached directly," said Edenhofer. "Oct4 activates the process, destabilizes the cells and clears them for the direct reprogramming. However, we still need to analyze the exact mechanism of the cellular conversion."

The scientists at the University of Bonn have thus found a new way to reprogram cells, which is considerably faster and also safer in comparison to the iPS cells and embryonic stem cells. "Since we cut down on the reprogramming of the cells via the embryonic stage, our method is about two to three times faster than the method used to produce iPS cells," stresses Edenhofer. Thus the work involved and the costs are also much lower. In addition, the novel Bonn method is associated with a dramatically lower risk of tumors. As compared to other approaches, the Bonn scientists' method stands out due to the production of neural cells that can be multiplied to a nearly unlimited degree.

Low risk of tumor and unlimited self renewal

A low risk of tumor formation is important because in the distant future, neural cells will replace defective cells of the nervous system. A vision of the various international scientific teams is to eventually create adult stem cells for example from skin or hair root cells, differentiate these further for therapeutic purposes, and then implant them in damaged areas. "But that is still a long way off," says Edenhofer. However, the scientists have a rather urgent need today for a simple way to obtain brain stem cells from the patient to use them to study various neurodegenerative diseases and test drugs in a Petri dish. "Our work could form the basis for providing practically unlimited quantities of the patient's own cells." The current study was initially conducted on mice. "We are now extremely eager to see whether these results can also be applied to humans," says the Bonn scientist.

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A new shortcut for stem cell programming

Stem-Cell Trial Failed to Treat Heart Failure

SATURDAY, March 24 (HealthDay News) -- An innovative approach using patients' own bone marrow cells to treat chronic heart failure came up short in terms of effectiveness, researchers report.

Use of stem cell therapy to repair the slow, steady damage done to heart muscle and improve heart function is safe, but has not been shown to improve most measures of heart function, the study authors said.

"For the measures we paid most attention to, we saw no effect, there is no question about that," said researcher Dr. Lemuel Moye, a professor of biostatistics at the University of Texas School of Public Health in Houston.

"Ultimately, this is going to pay off handsomely for individuals and for public health in general, but it's going to take years of work," Moye said. "We are the vanguard looking for new promising lines of research."

While the hoped-for results didn't materialize, there appeared to be a small improvement in some patients, he said. "When we looked at another commonly used measure of heart function called ejection fraction, or the strength of the heart's pumping, that's where all the action was," Moye noted.

It's hard to know which measures of heart function to look at, Moye explained. "We have had some difficulty with that," he said.

Future research will look at other measures of heart function, pay more attention to the characteristics of the cells that are injected and determine which cells are best, he added.

Cardiac cells and other types of specially prepared cells are available now that were not accessible when this study started in 2009, Moye pointed out.

The results of the trial, which was sponsored by the U.S. National Heart, Lung, and Blood Institute, were to be presented Saturday at the American College of Cardiology's annual meeting in Chicago. The report was also published online March 24 in the Journal of the American Medical Association.

For the study, Moye and colleagues worked with 92 patients, average age 63 and mostly male, who had heart failure with and without chest pain. They were randomly assigned to receive either an injection of 100 million bone marrow cells from their own bone marrow, or an inactive placebo. Patients in both groups also received aggressive medical therapy.

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Stem-Cell Trial Failed to Treat Heart Failure

Cell therapy using patient's own bone marrow may present option for heart disease

Public release date: 24-Mar-2012 [ | E-mail | Share ]

Contact: Kristin Wincek kwincek@mhif.org 612-863-0249 Minneapolis Heart Institute Foundation

CHICAGO Cell therapy may present an option for patients with ischemic heart disease to use their own bone marrow cells to repair the damaged areas of their hearts, and may pave the way for future treatment options, according to the FOCUS trial, which will be presented as a late-breaking clinical trial March 24 at the 61st annual American College of Cardiology (ACC) scientific session.

This is the largest study to date to look at stem cell therapy, using a patient's own stem cells, to repair damaged areas of the heart in patients with chronic ischemic heart disease and left ventricular dysfunction. Researchers found that left ventricular ejection fraction (the percentage of blood leaving the heart's main pumping chamber) increased by a small but significant amount (2.7 percent) in patients who received stem cell therapy. The study also revealed that the improvement in ejection fraction correlated with the number of progenitor cells (CD34+ and CD133+) in the bone marrow; and this information will help in evaluating and designing future therapies and trials.

"FOCUS is an incredibly important trial, as it has informed the cell therapy community how to better treat this high-risk patient population, and allows us to enter into an exciting, next generation of stem cell therapy armed with more data," said study investigator Timothy D. Henry, MD, an interventional cardiologist at the Minneapolis Heart Institute (MHI) at Abbott Northwestern Hospital in Minneapolis and director of research with the Minneapolis Heart Institute Foundation.

This multicenter study was conducted by the Cardiovascular Cell Therapy Research Network (CCTRN), which is supported through a research grant from the National Institutes of Health's National, Heart, Lung and Blood Institute (NHLBI), with the goal to evaluate novel stem cell-based treatment strategies for individuals with cardiovascular disease.

FOCUS will be presented at ACC.12 by its lead investigator Emerson C. Perin, MD, PhD, director of clinical research for cardiovascular medicine at the Texas Heart Institute, one of the five sites in the CCTRN. The Minneapolis Heart Institute is another site of the five in the network, and a large number of CCTRN patients were enrolled in Minnesota.

For this study, which took place between April 2009 and April 2011, the five sites randomly selected 92 patients to receive stem cell treatment or placebo. The symptomatic patients, with an average age 63, all had chronic ischemic heart disease and an ejection fraction of less than 45 percent (baseline 34 percent) along with heart failure and/or angina and were no longer candidates for revascularization. "These patients had no other options, as medical management failed to improve their symptoms," explained the study's co-investigator Jay Traverse, MD, an interventionalist cardiologist at the Minneapolis Heart Institute at Abbott Northwestern Hospital and physician researcher with the Minneapolis Heart Institute Foundation.

Bone marrow was aspirated from the patients and processed to obtain just the mononuclear fraction of the marrow. In patients randomly selected to receive stem cell therapy, physicians inserted a catheter into the heart's left ventricle to inject 100 million stem cells in more than 15 sites that showed damage on the electromechanical mapping image of the heart.

"Studies such as these are able to be completed much faster because of the team approach of the network" said Sonia I. Skarlatos, PhD, NHBLI's deputy director of the division of cardiovascular sciences and program director of CCTRN.

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Cell therapy using patient's own bone marrow may present option for heart disease

Chevy Hockenberry, Mercersburg, gets stem cell transplant at Hershey

A local toddler with a very rare disease has begun a long recovery in Penn State Hershey Childrens Hospital after chemotherapy and a stem cell transplant.

Chevy Hockenberry, the 23-month-old son of Lance Hockenberry and Melissa Johnson of Mercersburg, suffers from Hurlers syndrome, a rare inherited genetic disorder that if left untreated, causes death within five years.

People with Hurlers syndrome do not produce lysosomal alpha-L-iduronidase, an enzyme that helps break down long chains of sugar molecules. The long sugar chains build up in the body, damage internal organs and eventually lead to death.

The transplant

Chevy was diagnosed with Hurlers in January, but his symptoms started showing up long before that.

He was always sick, Johnson said by phone from Hershey. Chevy was always in and out of the hospital and had developed pneumonia and mild scoliosis.

Once he was diagnosed, the only treatment option for was a stem cell transplant.

Its not curable, Johnson said. But the stem cell transplant stops the progression.

The stem cells came from donated umbilical cords and Chevys parents because they are both carriers of Hurlers.

Chevy had multiple weeks of enzymes infusion followed by nine days of chemotherapy before the stem cell transplant.

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Chevy Hockenberry, Mercersburg, gets stem cell transplant at Hershey