Brief review
Stem Cells in Adult Skeletal Muscle

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Abstract

Muscle satellite cells are a self-renewing pool of stem cells that give rise to daughter myogenic precursor cells in adult skeletal muscle, where they function in postnatal tissue growth and regeneration. Adult skeletal muscle also contains a novel stem cell population purified as a side population (SP), which actively excludes Hoechst 33342 dye. Muscle SP cells that express the hematopoietic stem cell marker Sca-1 possess the ability to differentiate into hematopoietic cells, skeletal muscle, and satellite cells following transplantation. The muscle SP fraction also contains cells expressing the hematopoietic marker CD45 that are capable of differentiation into hematopoietic cells and muscle cells. Thus, these novel muscle stem cells appear to have characteristics similar to those of hematopoietic stem cells, and can participate in muscle regeneration. This review outlines recent findings regarding different stem cell populations in skeletal muscle, and discusses their involvement in muscle regeneration.

Section snippets

Muscle Hematopoietic Potential Cells and Muscle Regeneration

Goodell et al. (1996) were the first to demonstrate that HSCs in bone marrow from many different species can be purified by fluorescence-activated cell sorting (FACS) of side population (SP) cells. The SP fraction of cells excludes Hoechst 33342 dye through the activity at the cell surface of multidrug resistance-like proteins such as BCRP1/ABCG2 Zhou et al. 2001, Zhou et al. 2002. Gussoni et al. (1999) then showed that these bone marrow SP cells have the capacity to contribute to skeletal

Other Stem Cells in Muscle

During development, it is conceivable that the vascular-associated progenitors of myogenic satellite cells, termed meso-angioblasts in the embryo by De Angelis, Minasi and colleagues, persist in close association with the vasculature as adult stem cells in skeletal muscle De Angelis et al. 1999, Minasi et al. 2002. In addition, connective tissues in skeletal muscle have been reported to contain mesenchymal progenitor cells (Young et al. 2001). Recently, several groups have isolated a

Future Directions

Induction of myogenic specification of stem cells in muscle may involve one or more mechanisms, including secreted factor(s), extracellular matrix, and cell–cell interactions. The molecular mechanism of myogenic specification of these stem cells will be elucidated by combining information from in vitro culture systems and different animal systems, including genetic analysis afforded by gene knockout experiments. Undoubtedly, muscle possesses multiple stem cell populations, for which

Acknowledgements

The author would like to thank M.A. Rudnicki, J. Ishibashi, and S. Morita for critical reading of the manuscript. This work was supported by a development grant from the Muscular Dystrophy Association to A.A.

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