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First published online 8 April 2008
doi: 10.1242/jcs.021675

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

Eric S. Luth^1,*, Susan J. Jun², McKenzie K. Wessen¹, Kalliopi Liadaki^1,3,, Emanuela Gussoni¹ and Louis M. Kunkel^1,3,

¹ Program in Genomics, Division of Genetics, Children's Hospital Boston, Boston, MA 02115, USA
² Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
³ Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA 02115, USA

Author for correspondence (e-mail: kunkel{at}enders.tch.harvard.edu)

Accepted 1 February 2008

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 β-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.

Key words: Skeletal Muscle, Bone Marrow, Side Population, Progenitor