Mesenchymal stem cell therapy following muscle trauma leads to improved muscular regeneration in both male and female rats

Abstract

Background: Mesenchymal stem cell (MSC) therapy has the potential to enhance muscular regeneration. In previous publications, our group was able to show a dose-response relationship in female animals between the amount of transplanted cells and muscle force. The impact of sex on the regeneration of musculoskeletal injuries following MSC transplantation remains unclear.

Objective: We investigated histologic and biomechanical regeneration parameters in rats after autologous transplantation of MSCs. Our hypothesis was that female rats have greater muscle regeneration potential than male rats after autologous MSC transplantation.

Methods: Thirty-six Sprague-Dawley rats received an open crush trauma of the left soleus muscle. One week after trauma, 2.5 × 10(6) autologous MSCs, harvested from tibial biopsies, were transplanted locally (female, n = 9; male, n = 9). Control animals received saline solution (female, n = 9; male, n = 9). Histologic analysis and biomechanical evaluation by in vivo muscle force measurement were performed 3 weeks after transplantation.

Results: MSC therapy improved the force of the injured soleus in male rats significantly (twitch: treated, 0.76 [0.51-1.15]; twitch: untreated, 0.45 [0.32-0.73] [P = 0.01]; tetany: treated, 0.63 [0.4-1.21], tetany: untreated, 0.34 [0.16-0.48] [P = 0.04]). Force measurements in females also revealed significant improvements (twitch: treated, 0.71 [0.38-0.96]; twitch: untreated, 0.36 [0.18-0.63] [P = 0.005]; tetany: treated, 0.53 [0.21-0.68]; tetany: untreated, 0.27 [0.11-0.47] [P = 0.01]). The intersexual comparison of fast twitch and tetanic contraction forces revealed no significance (twitch, P = 0.55; tetany, P = 0.19). The histologic analysis showed no differences in the amount of fibrotic tissue (male, P = 0.9; female, P = 0.14) and the size of muscle area (male, P = 0.2; female, P = 0.56) following treatment. Male animals showed higher values for muscle area (P = 0.011) and less fibrosis (P = 0.028), independent of treatment.

Conclusion: The outcome of skeletal muscle regeneration after injury can be improved in animals of both sexes with MSC transplantation.