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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1488-1494.
Prepublished online as a Blood First Edition Paper on May 3, 2005; DOI 10.1182/blood-2005-01-0264.


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TRANSPLANTATION

Critical variables in the conversion of marrow cells to skeletal muscle

Mehrdad Abedi, Deborah A. Greer, Bethany M. Foster, Gerald A. Colvin, Joshua A. Harpel, Delia A. Demers, Jeffery Pimentel, Mark S. Dooner, and Peter J. Quesenberry

From the Roger Williams Medical Center, Department of Research, Providence, RI.

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. (Blood. 2005;106:1488-1494)


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