Intramuscular transplantation and survival of freshly isolated bone marrow cells following skeletal muscle ischemia-reperfusion injury

BACKGROUND: Delayed treatment cellular therapies offer an attractive means to treat extremity injuries involving acute skeletal muscle ischemia-reperfusion injury (I/R). Bone marrow is a rich source of stem and progenitor cells with the potential to improve skeletal muscle regeneration. The extent to which bone marrow cells (BMCs) may be useful for I/R is not known. The purposes of this study were twofold: (1) to evaluate BMC survival following intramuscular injection 0, 2, 7, and 14 days after injury and (2) to determine whether BMCs improve functional recovery following I/R. METHODS: Magnetic-activated cell sorting was used to isolate lineage-negative (Lin) BMCs and enrich for stem and progenitor cells. To evaluate in vivo cell survival following I/R, Lin BMCs were injected intramuscularly 0, 2, 7, and 14 days after I/R, and bioluminescent imaging was performed for up to 28 days after cell injections. To assess their ability to improve muscle regeneration, intramuscular injections were performed 2 days after injury, and in vivo muscle function was assessed 14 days later. RESULTS: Lin BMCs survived throughout the study period regardless of the timing of delivery. Intramuscular injection of Lin BMCs did not improve maximal isometric torque (300 Hz); however, both saline-injected and Lin BMC-injected muscles exhibited an increase in the twitch-tetanus ratio, suggesting that damage incurred with the intramuscular injections may have had deleterious consequences for functional recovery. CONCLUSION: Although BMCs injected intramuscularly survived cell transplantation, they failed to improve muscle function following I/R. The ability of BMCs to persist in injured muscle following I/R lends to the possibility that with further development, their full potential can be realized.