Evaluation of Sca-1 and c-Kit as selective markers for muscle remodelling by nonhemopoietic bone marrow cells.
Bone marrow (BM)-derived cells (BMCs) have demonstrated a myogenic tissue remodeling capacity. However, because the myoremodeling is limited to approximately 1%-3% of recipient muscle fibers in vivo, there is disagreement regarding the clinical relevance of BM for therapeutic application in myodegenerative conditions. This study sought to determine whether rare selectable cell surface markers (in particular, c-Kit) could be used to identify a BMC population with enhanced myoremodeling capacity. Dystrophic mdx muscle remodeling has been achieved using BMCs sorted by expression of stem cell antigen-1 (Sca-1). The inference that Sca-1 is also a selectable marker associated with myoremodeling capacity by muscle-derived cells prompted this study of relative myoremodeling contributions from BMCs (compared with muscle cells) on the basis of expression or absence of Sca-1. We show that myoremodeling activity does not differ in cells sorted solely on the basis of Sca-1 from either muscle or BM. In addition, further fractionation of BM to a more mesenchymal-like cell population with lineage markers and CD45 subsequently revealed a stronger selectability of myoremodeling capacity with c-Kit/Sca-1 (p < .005) than with Sca-1 alone. These results suggest that c-Kit may provide a useful selectable marker that facilitates selection of cells with an augmented myoremodeling capacity derived from BM and possibly from other nonmuscle tissues. In turn, this may provide a new methodology for rapid isolation of myoremodeling capacities from muscle and nonmuscle tissues. Disclosure of potential conflicts of interest is found at the end of this article.
Wong
Sharon H A
SH
National Muscular Dystrophy Research Centre, Department of Clinical Neurosciences, St. Vincent's Hospital, 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia.
Lowes
Kym N
KN
Bertoncello
Ivan
I
Quigley
Anita F
AF
Simmons
Paul J
PJ
Cook
Mark J
MJ
Kornberg
Andrew J
AJ
Kapsa
Robert M I
RM
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002458:Cell Fractionation; D005434:Flow Cytometry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D024510:Muscle Development / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D009132:Muscles / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis* / Q000378:metabolism; D012038:Regeneration
D000950:Antigens, Ly; D015415:Biomarkers; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit