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