Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: a multifactorial process.
OBJECTIVE
Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion.


METHODS
We transplanted green fluorescence protein (GFP)-transgenic marrow into irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin. One month after injury, sections were analyzed by standard and deconvolutional microscopy for expression of muscle and hematopoietic markers.


RESULTS
Irradiation was essential to conversion, although whether by injury or induction of chimerism is not clear. Cardiotoxin- and, to a lesser extent, PBS-injected muscles showed significant number of GFP(+) muscle fibers, while uninjected muscles showed only rare GFP(+) cells. Marrow conversion to muscle was increased by two cycles of G-CSF mobilization and to a lesser extent by G-CSF and steel or GM-CSF. Transplantation of female GFP to male C57BL/6 and GFP to ROSA26 mice showed fusion of donor cells to recipient muscle. High numbers of donor-derived muscle colonies and up to 12% GFP(+) muscle cells were seen after mobilization or direct injection. These levels of donor muscle chimerism approach levels that could be clinically significant in developing strategies for the treatment of muscular dystrophies.


CONCLUSIONS
In summary, the conversion of marrow to skeletal muscle cells is based on cell fusion and is critically dependent on injury. This conversion is also numerically significant and increases with mobilization.
Abedi
Mehrdad
M
Roger Williams Medical Center, Department of Research, Providence, RI 02864, USA. mabedi@rwmc.org
Greer
Deborah A
DA
Colvin
Gerald A
GA
Demers
Delia A
DA
Dooner
Mark S
MS
Harpel
Jasha A
JA
Weier
Heinz-Ulrich
HU
Lambert
Jean-Francois
JF
Quesenberry
P J
PJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002459:Cell Fusion; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins; D019650:Hematopoietic Stem Cell Mobilization; D008164:Luminescent Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000166:cytology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D018482:Muscle, Skeletal / Q000293:injuries; D012038:Regeneration; D018183:Transplantation Chimera
D003115:Colony-Stimulating Factors; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins