Revolutionary Findings Prove Novel Mechanism of Stem Cells

Miller School researchers have demonstrated exactly how mesenchymal stem cells from bone marrow can repair the heart – a critical step in stem cell research that could in the near future help millions of patients with heart failure.

The findings, published in the July 29 issue of Circulation Research, a journal of the American Heart Association, address an area that has been of enormous interest to cardiologists since the first suggestion that bone marrow-derived mesenchymal stem cells regenerate heart muscle damaged by a myocardial infarction (heart attack). Joshua M. Hare, M.D., director of the Interdisciplinary Stem Cell Institute at the Miller School, led the discovery which settles several major controversies in the field and shows that the stem cells used can restore heart function back to normal very rapidly after heart attack.

The stem cell field has been plagued by a controversy surrounding exactly how bone marrow cells repair damaged hearts. In this study Hare’s group shows that the cells not only turn into new heart muscle themselves (acting as true stem cells) but also stimulate the body’s own cardiac stem cells to go into overdrive to contribute to the repair process. These findings settle one of the most controversial areas of medicine – why the heart’s own stem cells are not able to fully repair heart damage. By showing that the MSCs can stimulate the heart’s own cells, the researchers have shown that in fact the body can repair itself if given the right kind of help.

The research is of particular importance as these cells have already been tested for safety in patients with heart attack and are undergoing additional testing right now for patients with heart failure.

This team hypothesized that MSCs encourage cardiac repair by stimulating cardiac stem cells (which are already present in the adult heart, and appear to be precursor cells to heart muscle) both to multiply and to differentiate into the hard-working heart muscle cells called cardiac myocytes, which then begin to “beat” or contract. Working with animal models, the researchers induced a heart attack (myocardial infarction). Three days later, the hearts were treated by injection directly into the damaged heart muscle, either with MSCs, or with the fluid medium containing MSC-secreted chemicals but no cells, or with a placebo.

The University of Miami team found that MSCs “facilitate substantial cardiac recovery,” producing both cardiac myocytes and blood vessel structures in two ways. Some of the MSCs differentiated into cardiac cells. Secondly, the MSCs appeared to cause cardiac stem cells to multiply and to differentiate themselves into cardiac cells.

“This shifts the paradigm of stem cell research,” says Hare. “For the first time, we’ve been able to demonstrate the exact mechanism of how mesenchymal stem cells stimulate the growth of new cardiac cells. The findings have implications for the entire field of regenerative medicine and show that the optimal therapies involve cells working together, rather than using only single cell types.”

In the animals that were treated with mesenchymal stem cells, there was a 20-fold increase in cardiac stem cells. When examined in vitro, MSCs stimulated cardiac stem cell proliferation into enriched populations of adult cardioblasts.

Alan W. Heldman, M.D., a professor of medicine and member of the Interdisciplinary Stem Cell Institute, was the interventional cardiologist who performed the catheter-based injections into the heart muscle. Heldman notes that this study “points out a totally new and intriguing aspect of working with this stem cell line.” The data indicate that MSCs generate new cardiomyocytes in the first 24 hours. Additionally, they stimulate a series of secondary responses that cause substantial amounts of adult and immature cardiomyocytes to proliferate and replenish the damaged regions of the heart.

“This points to a long-term effect that can pave the way for future therapies,” Heldman said. “We have known for several years that there is a measurable but very low rate of cell turnover in the adult heart; it seems that stem cell therapy may harness that natural phenomenon and accelerate it to the point that it becomes clinically important as a potential therapy.”

“As a clinician and researcher, this is very encouraging,” says Juan Pablo Zambrano, M.D., associate professor of medicine in the Cardiovascular Division. “This study and previous research continues to bear out the possibilities of generating cardiac repair using this stem cell line.”

“We continue to see evidence that mesenchymal stem cells have the ability to spur new cardiac muscle growth,” says Ian K. McNiece, Ph.D., professor of medicine and director of experimental and clinical therapies at the Interdisciplinary Stem Cell Institute.

Hare says this study, which was funded by grants from the National Heart, Lung, and Blood Institute, “reinforces our hypothesis that mesenchymal stem cells have enormous potential as a cell-based therapy for cardiac patients. The findings of this study support our ongoing program of developing this therapy for use in patients.”

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Very, very cool. Thanks Raktim.
Certainly topical at the moment........

Green light given to the world's first stem cell treatment on humans By David Gardner
The world's first experiments using embryonic stem cells to treat humans have been given the go-ahead in America.
California-based biotech firm Geron will begin clinical trials on patients paralysed by spinal cord injuries.

Scientists hope that injecting cells from discarded human embryos into the spines of volunteers will trigger regrowth of damaged nerve cells and eventually allow the patients to recover feeling and movement.
Breakthrough: Stem cell trials are to be undertaken on patients with spinal cord injuries
The Vatican condemned the controversial milestone as ' unacceptable' and anti-abortion groups say they are planning protests across the country.
The study was cleared by President Obama a year ago, but was put on hold because some animals on which the company was testing the treatment developed cysts. Now Geron claims it has overcome the problem.
Dr Richard Fessler, a neurological surgeon at Northwestern University who will lead the research, said that if the treatment works on humans it would be 'revolutionary'.
'The therapy would provide a viable treatment option for thousands of patients who suffer severe spinal cord injuries each year,' he said.
Geron has spent 15 years and more than £100million developing the treatment and hopes to begin the study within the next few months.
Adult stem cells, which typically produce a set variety of tissue types, have been tested on patients with limited success.
But researchers hope the use of highly versatile embryonic stem cells - which can turn into any cell in the body - will revolutionise medicine, from creating organs for transplants to helping to test drugs.
The therapy also has the potential to help patients with Alzheimer's disease and multiple sclerosis.
Until now, the ethical barrier of using discarded three- to five-day-old embryos has prevented any tests on humans.

The Bush administration, fearing a backlash from its many evangelical Christian supporters, kept embryonic stem cell research tightly shackled, but last year President Obama repealed the block.
The Roman Catholic Church remains fiercely opposed to the research. Vatican official Elio Dgreccia said: 'Despite the efforts that are made to deny it, science continues to show us that the embryo is a human being in the making.'
One of Britain's leading stem cell researchers, Dr Robin Lovell-Badge of the National Institute for Medical Research, said: 'It is critical that the first steps to using human embryonic stem cell-derived cells for treatments are carried out with caution.
'The last thing a field needs, especially one weighed down with so much ethical and political debate, is a disaster.
'However, while it is right to proceed with care, at some point someone has to be brave. Many treatments that are today routine began with both the clinical teams and the patients taking a gamble, whether it was Christiaan Barnard and heart transplants or Edwards and Steptoe with IVF.'

Read more:
And so it appears as tho embryonic stem cells have already fixed DMD mouse, at least according to this abstract:

PlosOne.2009;4(3):e4759.Epub 2009 Mar 11.
Dept of Cell Biology and Molecular Medicine, Univ of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey.
PMID: 19277212 (Pubmed - indexed for Medline)
This GOOD.Do I see some light here?
Seeing light here too. Not sure what it all means just yet since I recently asked Dr Flanigan about this abstract and he's never seen it. I do expect to have the opportunity to meet one of the researchers, Dr Fraidenraich, in a couple of months :)

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