The synergistic effect of treadmill running on stem-cell transplantation to heal injured skeletal muscle

Muscle-derived stem-cell (MDSC) transplantation presents a promising method for the treatment of muscle injuries. This study investigated the ability of exercise to enhance MDSC transplantation into the injured muscle. Mice were divided into four groups: contusion+phosphate-buffered saline (C+PBS; n=14 muscles), C+MDSC transplantation (n=12 muscles), C+PBS+treadmill running (C+PBS+TM; n=17 muscles), and C+MDSC+TM (n=13 muscles). One day after injury, the TM groups began running for 1 or 5 weeks. Two days after injury, muscles of C+MDSC and C+MDSC+TM groups were injected with MDSCs. One or 5 weeks later, the number and differentiation of transplanted MDSCs, myofiber regeneration, collagen I formation, and vascularity were assessed histologically. In vitro, MDSCs were subjected to mechanical stimulation, and growth kinetics were quantified. In vitro, mechanical stimulation decreased the MDSC population doubling time (18.6±1.6h) and cell division time (10.9±0.7h), compared with the controls (population doubling time: 23.0±3.4h; cell division time: 13.3±1.1h) (p=0.01 and 0.03, respectively). In vivo, 5 weeks of TM increased the myogenic contribution of transplanted MDSCs, compared with the controls (p=0.02). C+MDSC, C+PBS+TM, and C+MDSC+TM demonstrated decreased fibrosis at 5 weeks, compared with the C+PBS controls (p=0.00, p=0.03, and p=0.02, respectively). Results suggest that the mechanical stimulation favors MDSC proliferation, both in vitro and in vivo, and that exercise enhances MDSC transplantation after injury. © 2010 Mary Ann Liebert, Inc.