New evidence suggests that a promising investigational treatment for patients with damaged hearts -- using adult stem cells to regenerate heart tissue -- may not work as planned. In the December 2004 issue of the Journal of Clinical Investigation, researchers from the University of Chicago show that although stem cells derived from bone marrow can find their way to areas of damaged heart muscle, infiltrate into these regions and proliferate, they do not mature into new cardiac muscle cells.

A series of previous studies suggested that stem cells from bone marrow could be induced to become cardiac muscle, replacing damaged tissue and potentially restoring heart function. This series of more-rigorous experiments, however, found that the transplanted cells are unable to take the crucial final steps. They do not produce a muscle protein called sarcoglycan, which is necessary for normal heart and skeletal muscle function.

The failure of these cells to express this protein "severely limits their utility for cardiac and skeletal muscle regeneration," the authors note.

"This was a complete surprise, and a considerable disappointment," said study director Elizabeth McNally, M.D., Ph.D., associate professor of medicine at the University of Chicago. "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."

The researchers used bone marrow side population cells (BM-SP), a sub-set of the stem cells found in marrow. Earlier studies demonstrated that these cells could home in on areas of damaged muscle and suggested that they matured into working skeletal or cardiac muscle cells. Clinical trials of this approach are already underway in patients who have had a heart attack and initial results have been "promising."

Despite high hopes for such cellular self-renewal, howev
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Contact: John Easton
John.Easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
1-Dec-2004

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