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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.
Submitted January 19, 2005
Department of Research, Roger Williams Medical Center, Providence, RI, USA * Corresponding author; email: mabedi{at}rwmc.org.
We have studied conversion of marrow cells to skeletal muscle in cardiotoxin injured anterior tibialis muscle in a GFP to C57BL/6 transplant model and ascertained that total body irradiation (TBI) with establishment of chimerism is a critical factor. Local irradiation has little impact in lower doses and was detrimental at higher doses. 1000cGy of whole body with shielding the leg or a combination of 500 cGy TBI and 500 cGy local radiations was found to give the best results. In 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 transplant 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.
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