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Although the contribution of bone marrow-derived cells to regenerating skeletal muscle has been repeatedly documented, there remains considerable debate as to whether this incorporation is exclusively a result of inflammatory cell fusion to regenerating myofibers or whether certain populations of bone marrow-derived cells have the capacity to differentiate into muscle. The present study uses a dual-marker approach in which GFP(+) cells were intravenously transplanted into lethally irradiated beta-galactosidase(+) recipients to allow for simple determination of donor and host contribution to the muscle. FACS analysis of cardiotoxin-damaged muscle revealed that CD45(+) bone-marrow side-population (SP) cells, a group enriched in hematopoietic stem cells, can give rise to CD45(-)/Sca-1(+)/desmin(+) cells capable of myogenic differentiation. Moreover, after immunohistochemical examination of the muscles of both SP- and whole bone marrow-transplanted animals, we noted the presence of myofibers composed only of bone marrow-derived cells. Our findings suggest that a subpopulation of bone marrow SP cells contains precursor cells whose progeny have the potential to differentiate towards a muscle lineage and are capable of de novo myogenesis following transplantation and initiation of muscle repair via chemical damage.

Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation