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Study dashes hopes of using adult stem cells to rebuild heart

University Of Chicago : 21 July, 2001  (Technical Article)
Researchers reported that bone marrow stem cells were unable to regenerate damaged heart tissue in laboratory animals, suggesting that a proposed revolutionary therapy for the 1.1 million Americans who suffer heart attacks each year may be destined to fail.
The study is the latest to cast doubts on the scientific dream that a patient's own mature stem cells, instead of stem cells from emyos, could someday be used to replace cells damaged or missing because of genetic diseases, tissue injuries or degenerative illnesses.

Earlier studies had been very optimistic about the capability of bone marrow stem cells to be coaxed into growing new heart cells so that a weakened heart could regain its pumping power.

'This was a complete surprise and a considerable disappointment,' said Dr. Elizabeth McNally, a University of Chicago researcher and cardiologist who directed the study with colleagues from the U. of C. and the University of California, San Francisco.

Results of the study were published in the Journal of Clinical Investigation.

'We set out to confirm, using more stringent criteria, the very appealing strategy of using stem cells from bone marrow to regenerate cardiac muscle, but we found that they never become normal, mature muscle cells,' McNally said.

Scientists previously had demonstrated that these cells, which normally make blood, could home in on areas of damaged muscle and suggested they matured into working heart or muscle cells.

Animal experiments were so encouraging that human clinical trials are under way with heart attack and congestive heart failure victims.

Working with mice, the McNally team found that the bone marrow stem cells found their way to areas of damaged heart muscle, infiltrated these regions and proliferated. But they failed to take the crucial final steps and produce sarcoglycan, a muscle protein essential for normal heart and skeletal muscle function.

The transplants spurred the development of new blood vessels to the heart, which was beneficial.

'But the mice also developed abnormal cardiac rhythms, meaning the cells were not making normal electrical connections as real heart cells do,' McNally said.

'Our experiments clearly show that the transplanted cells aren't growing, as we once hoped, into heart cells. But they may stimulate the growth of new blood vessels into the damaged regions or they may secrete growth factors that promote recovery.

'If we can figure out what is actually going on with the human patients and understand the mechanism, we might be able to design a more effective approach.'

Other stem cell researchers praised the work, even if the results challenged cherished assumptions.

'Although there have been a number of studies suggesting that transplantation of bone marrow stem cells ... can be used to repair organs such as the heart and brain, there has not been good evidence that such cells can generate normal tissue, such as heart muscle cells,' said Dr. John Kessler, chief of neurology at Northwestern University.

'This carefully done study reinforces this point. It also highlights the need to continue studies of other cell types such as embryonic stem cells that clearly do have the capacity to differentiate into cardiac muscle cells and other cell types.'

Dr. Ronald McKay, a pioneering stem cell researcher at the National Institutes of Health, is trying to use bone marrow stem cells to make new brain cells, and he said the jury is still out on whether or not it can be achieved. 'There are interesting data in brain experiments that make me optimistic that we will see progress in the long term,' he said.

Heart cells seem to be the hardest cells for stem cell scientists to make, according to a prominent researcher of cell- and gene-based therapies, Dr. Doris Taylor, director of the Center for Cardiovascular Repair at the University of Minnesota.

'If we transplanted too many new cells in the heart, it would destroy the geometry and cause a catastrophe. So nature puts on the brakes and won't let us,' said Taylor, who with other researchers has shown that some adult stem cells in bone marrow can develop into other kinds of cells.

Researchers may disagree about the possibilities of adult stem cells, but in general Taylor considers the new study to be good news.

'It brings a new level of rigor to the field and tells us this is not going to be as easy as many of us had thought,' she said.
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