Intramuscular Transplantation of Muscle-Derived Stem Cells Accelerates Skeletal Muscle Healing After Contusion Injury via Enhancement of Angiogenesis

Background: Muscle contusions are common muscle injuries. Although these injuries are capable of healing, incomplete functional recovery often occurs. Muscle-derived stem cells (MDSCs) are likely derived from blood vessel cells and have a multilineage differentiation potential. Purpose: The aims of this study are (1) to find optimal timing of MDSC transplantation to enhance muscle healing by stimulating muscle regeneration and preventing scar tissue (fibrosis) formation after skeletal muscle contusion injury, and (2) to investigate the role of angiogenesis in the muscle-healing process after MDSC transplantation. Study Design: Controlled laboratory study. Methods: Muscle-derived stem cells were injected directly into injured tibialis anterior muscles of mice at various time points (1, 4, and 7 days) after the muscle contusion injury. Muscle regeneration, angiogenesis, and fibrosis formation were evaluated by histology and real-time polymerase chain reaction analysis, and functional recovery was measured by physiologic testing. Results: Transplantation of MDSCs at 4 days after injury significantly promoted angiogenesis, which was induced by high levels of vascular endothelial growth factor expression at week 1, and significantly increased muscle regeneration and muscle strength by week 2, when compared with the other groups. A decrease in fibrosis formation was observed at week 4, when compared with the other groups, after the transplantation of MDSCs at 4 and 7 days after injury. Conclusion: Intramuscular injection of MDSCs at 4 days after injury improved and accelerated skeletal muscle healing by increasing angiogenesis and decreasing scar tissue formation. Clinical Relevance: These findings could contribute to the development of biologic treatments to aid in muscle healing after muscle injury.