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First published online 30 March 2004
doi: 10.1242/jcs.01051

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Role of bone marrow cell trafficking in replenishing skeletal muscle SP and MP cell populations

François Rivier^1,*,, Ozan Alkan^2,, Alan F. Flint¹, Kristina Muskiewicz¹, Paul D. Allen³, Philippe Leboulch³ and Emanuela Gussoni^1,

¹ Division of Genetics, Children's Hospital Boston, MA 02115, USA
² Massachusetts Institute of Technology, Harvard-MIT Division of Health Sciences and Technology, 45 Carleton Street, Building E25, Room 529, Cambridge, MA 02139, USA
³ Department of Anesthesia, Brigham and Women's Hospital, Boston, MA 02115, USA

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

Accepted 9 December 2003

The multipotent nature of skeletal muscle-derived side population cells is demonstrated by their myogenic and hematopoietic potential in vivo. However, whether muscle side population cells are derived from the bone marrow is unclear. To study the long-term contribution of the hematopoietic system to muscle side population, whole bone marrow cells from Ly5.1 males or from e-GFP transgenic male mice were transplanted into lethally irradiated Ly5.2 females. Long-term cell trafficking of donor bone marrow cells to muscle side population was monitored 17 times in a 34-week study. Fluorescence-activated cell sorter analyses were used to detect Ly5.1 and GFP⁺ donor cells, which were confirmed by fluorescence in situ hybridization of the Y-chromosome. Analyses post-transplantation indicated that whereas cells of donor origin could be found in the muscle, donor bone marrow cells had contributed little to the muscle side population. Attempts to increase cell trafficking by induced muscle damage again confirmed that more than 90% of side population cells present in the muscle were derived from the host. These results demonstrate that muscle side population cells are not replenished by the bone marrow and suggest a non-hematopoietic origin for this cell population.

Key words: Muscle side population, Cell trafficking, Bone marrow transplantation, Fluorescence activated cell sorter (FACS)

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