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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 +/- 1.6 h) and cell division time (10.9 +/- 0.7 h), compared with the controls (population doubling time: 23.0 +/- 3.4 h; cell division time: 13.3 +/- 1.1 h) (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.

Unlabelled: The effects of different mobilization protocols for muscle regeneration after myotoxin injury was compared in the rat tibialis anterior (TA) muscle. Adult Wistar rats were divided into control (C); mobilized (M); injury (I); injury + late mobilization (LM) and injury + early mobilization (EM) groups. Muscle injury was induced by intramuscular lidocaine injection. The exercised animals were mobilized for 5 and 8 days during 15 and 45 minutes/session. The swimming started 1 hour or 3 days after injury. All animals were killed 8 days after the injury, together with the control group, when the TA muscles were weighted and excised. Cross sections were obtained by cryostat and submitted to Toluidine Blue stain. Qualitative morphological characterization of muscle regeneration and quantitative analysis of muscle fiber and non-muscle fiber area density were performed. The I and late mobilization groups showed decreased muscle mass when compared to all other groups. All injured animals showed signs of muscle fiber damage, although signs of early regenerated muscle fibers were more evident in injury + mobilization groups. Only the EM groups submitted to 45 minutes of exercise had increased muscle fiber and decreased non-muscle fiber area density values when compared to I group (p<0.05)., Conclusion: the regeneration process is related to the onset of exercise, since animals submitted to early mobilization showed improved regeneration when comparted to LM groups. Besides, the length of session is also important for accelerating the regeneration process, as it was observed that 45 minutes was better than 15 minutes duration.