Critical variables in the conversion of marrow cells to skeletal muscle.
We have studied conversion of marrow cells to skeletal muscle in cardiotoxin-injured anterior tibialis muscle in a green fluorescent protein (GFP) to C57BL/6 transplantation model and ascertained that total body irradiation (TBI) with establishment of chimerism is a critical factor. Local irradiation has little effect in lower doses and was detrimental at higher doses. Whole body (1000 cGy) with shielding of the leg or a combination of 500 cGy TBI and 500 cGy local radiations was found to give the best results. In non-obese diabetic-severe combined immunodeficient (NOD-SCID) recipients, we were able to show that conversion could occur without radiation, albeit at relatively lower levels. Within 3 days of cardiotoxin injury, GFP-positive mononuclear cells were seen in the muscle, and within 2 weeks GFP-positive muscle fibers were identified. Conversion rates were increased by increasing donor-cell dose. Timing of the cardiotoxin injury relative to the transplantation was critical. These studies show that variables in transplantation and injury are critical features of marrow-to-muscle conversions. Irradiation primarily effects conversion by promoting chimerism. These data may explain the differences in the literature for the frequency of marrow-to-skeletal muscle conversion and can set a platform for future models and perhaps clinical protocols.
Abedi
Mehrdad
M
Department of Research, Roger Williams Medical Center, 825 Chalkstone Ave, Providence, RI 02908-4735, USA. mabedi@rwmc.org
Greer
Deborah A
DA
Foster
Bethany M
BM
Colvin
Gerald A
GA
Harpel
Joshua A
JA
Demers
Delia A
DA
Pimentel
Jeffery
J
Dooner
Mark S
MS
Quesenberry
Peter J
PJ
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D004307:Dose-Response Relationship, Radiation; D049452:Green Fluorescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D012038:Regeneration; D013997:Time Factors; D018183:Transplantation Chimera; D014916:Whole-Body Irradiation
D049452:Green Fluorescent Proteins