Treatment of Tourniquet-Induced Ischemia Reperfusion Injury with Muscle Progenitor Cells

Abstract

Acute ischemia reperfusion injury (IRI) results in muscle atrophy and functional loss. Although studies have shown that stem cells can improve muscle function in chronic ischemia caused by vascular diseases, none investigated whether stem cells can improve muscle function following acute IRI. The primary purpose of this study was to determine whether transplantation of muscle progenitor cells (MPCs) improves recovery of muscle function after tourniquet (TK) induced IRI. IRI was induced in rat hind limb muscles with a pneumatic TK (250 mmHg) for 3 h. Rats were then divided into two groups; receiving either intramuscular injection of MPCs or vehicle control into the injured tibialis anterior muscle 48 h after tourniquet application. Muscle mass, isometric contractile properties, and selected histologic properties were evaluated at 2 wk after ischemia. IRI resulted in significant reductions in absolute muscle force (N) and specific muscle force (N/cm(2)). MPC treatment significantly prevented the loss in muscle specific force compared with vehicle controls. The mass and cross sectional areas of the muscles were similar between treatment groups. Histologic results showed that a small number of transplanted cells differentiated and formed muscle fibers, which could potentially contribute to force generation. IRI caused significant fibrosis and inflammation, both of which could affect muscle-specific force, of which inflammation was reduced by MPCs treatment. Intramuscular injection of MPCs may provide a beneficial treatment for improving functional recovery following IRI, and the beneficial effects are mainly through improving muscle quality (specific force) but not quantity (mass).