Evaluation of Sca-1 and c-Kit as selective markers for muscle remodelling by non-hemopoietic bone marrow cells

¹ National Muscular Dystrophy Research Centre, Fitzroy, Victoria, Australia; Howard Florey Institute, Parkville, Victoria, Australia; Department of Medicine, The University of Melbourne, Fitzroy, Victoria, Australia
² National Muscular Dystrophy Research Centre, Fitzroy, Victoria, Australia; Howard Florey Institute, Parkville, Victoria, Australia; Department of Medicine, The University of Melbourne, Fitzroy, Victoria, Australia; The Bionic Ear Institute, East Melbourne, Victoria, Australia
³ Stem Cell laboratory, Peter McCallum Cancer Research Institute, East Melbourne, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia; Australian Stem Cell Centre Ltd, Monash University, Clayton, Victoria, Australia
⁴ Department of Medicine, The University of Melbourne, Fitzroy, Victoria, Australia; Centre for Neurology and Neuroscience Research, St Vincent's Hospital, Fitzroy, Victoria, Australia
⁵ Peter MacCallum Cancer Centre, Stem Cell laboratory; The University of Texas, Center for Stem Cell Biology
⁶ National Muscular Dystrophy Research Centre, Fitzroy, Victoria, Australia; Howard Florey Institute, Parkville, Victoria, Australia; Department of Neurology and Royal Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia
⁷ National Muscular Dystrophy Research Centre, Fitzroy, Victoria, Australia; Howard Florey Institute, Parkville, Victoria, Australia; Department of Medicine, The University of Melbourne, Fitzroy, Victoria, Australia; Centre for Neurology and Neuroscience Research, St Vincent's Hospital, Fitzroy, Victoria, Australia; The Bionic Ear Institute, East Melbourne, Victoria, Australia

^* To whom correspondence should be addressed. E-mail: wongsh{at}svhm.org.au.

	Abstract

Bone marrow-derived cells (BMCs) have demonstrated a myogenic tissue remodeling capacity. However, because the myoremodeling is limited to around 1%-3% of recipient muscle fibers in vivo, there is disagreement regarding the clinical relevance of bone marrow (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 non-muscle tissues. In turn, this may provide a new methodology for rapid isolation of myoremodeling capacities from muscle and non-muscle tissues.