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Mesenchymal Stem Cell Therapy Following Muscle Trauma Leads to Improved Muscular Regeneration in Both Male and Female Rats
Affiliation:1. School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Center of Physical Therapy, National Taiwan University Hospital, Taipei, Taiwan;2. Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong;3. Department of Orthopaedics, Clintec, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;4. Department of Medical Image, National Taiwan University Hospital, Department of Surgery, College of Medicine, National Taiwan University, Taiwan;5. Department of Business Administration, Hwa Hsia Institute of Technology, Taipei, Taiwan
Abstract:BackgroundMesenchymal 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.ObjectiveWe 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.MethodsThirty-six Sprague-Dawley rats received an open crush trauma of the left soleus muscle. One week after trauma, 2.5 × 106 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.ResultsMSC 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.ConclusionThe outcome of skeletal muscle regeneration after injury can be improved in animals of both sexes with MSC transplantation.
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