Stem cells to the rescue - or not?

December 01, 2004

The use of stem cells obtained from bone marrow for the treatment of some skeletal or heart diseases is an attractive long-term strategy to deliver normal stem cells, capable of developing into any cell type of the body, to injured tissue in order to effect repair. A subset of bone marrow cells, called bone marrow-derived side population (BM-SP) cells, make up only 0.01-0.05% of whole bone marrow. In mice, these cells have previously been reported to restore expression of the protein that is lacking in muscular dystrophy. Many studies have shown that stem cells are able to home to injured skeletal and cardiac muscle, however in the past, marker proteins that show the location of donor stem cells within damaged tissue of the recipient have not been able to definitively distinguish between donor and recipient cells, which raises the possibility that the recipients own cells have in fact been responsible for observed regeneration.

In the December 1 issue of the Journal of Clinical Investigation, Elizabeth McNally and colleagues from the University of Chicago transplanted BM-SP cells from normal male mice into female mice lacking delta-sarcoglycan - an animal model of cardiomyopathy and muscular dystrophy - to determine whether these stem cells would be recruited to skeletal and cardiac muscle to restore delta -sarcoglycan expression. Surprisingly, upon examination of many thousands of muscle cells, the authors found that while donor cells readily engrafted into the delta -sarcoglycan-deficient cardiac and skeletal muscle (evidenced by the Y chromosome from male donor cells present within the recipient female muscle), these donor cells were only able to restore sarcoglycan expression in 2 muscle fibers. This finding demonstrates that BM-SP stem cells can produce delta -sarcoglycan but do so at a negligible degree, suggesting that they have a limited potential for cardiac and skeletal muscle regeneration.

In an accompanying commentary, Giulio Cossu, from the Stem Cell Research Institute in Milan discusses how this study "raises additional concerns relating to stem cell plasticity and stem cell therapy in an already heated and controversial field." This study stands in contrast to others that have claimed successful differentiation of BM-SP stem cells in specific tissues. Dr. Cossu offers some reasons for the experimental discrepancies and stresses that "it would be important to repeat the same experiments described here....with other types of stem cells...[as] they may represent a better perspective for the stem cell therapy of striated muscle diseases than BM-SP stem cells." In light of these data, McNally and colleagues suggest that "active pursuit of...alternative approaches should be fully investigated as we advance into regenerative medicine."
TITLE: Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression after engraftment into cardiac and skeletal muscle

Elizabeth McNally
Department of Medicine
University of Chicago
Chicago, Illinois, USA
Phone: 773-702-2672
Fax: 773-702-2681
View the PDF of this article at:


TITLE: Fusion of bone marrow-derived stem cells with striated muscle may not be sufficient to activate muscle genes

Giulio Cossu
Stem Cell Research Institute
DIBIT, Milan, Italy
Phone: 3902-2156-0250
Fax: 3902-2156-0220

JCI Journals

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