Biological intervention based on cell and gene therapy to improve muscle healing after laceration

Muscle laceration is a challenging problem in traumatology and is common in sports injuries, with functional recovery remaining slow and incomplete. Even though muscles retain their ability to regenerate after injury, muscles' healing process after such injuries has been found to be very slow and often leads to incomplete muscle recovery. Growth factors may have a role in enhancing recovery. Our previous study showed that IGF-1, β-FGF and NGF can improve myoblast proliferation and differentiation in vitro. We then investigated whether the delivery of IGF-1 would improve muscle healing after injuries. We observed that muscle regeneration was enhanced in lacerated muscles treated with IGF-1 protein, which consequently led to an improvement in muscle healing. However, the rapid clearance and short biological half-lives of these proteins may have limited the success of this approach. We then investigated the efficiency of gene therapy based on adenovirus to deliver a stable expression of the growth factor IGF-1. Although a slight improvement in the healing process occurred in the muscle injected with adenovirus (AIGF), the combination of myoblast transplantation and gene therapy with the ex vivo approach further improved the healing process. The injection of normal myoblasts into the injured muscle led to the best improvement of muscle healing at two weeks post-injection. Implantation of normal minced muscle into mdx mice was also capable of improving muscle healing at 2-4 weeks post-implantation. These studies will further our understanding of muscle healing post-injury and help in the development of strategies to promote efficient muscle healing and complete functional recovery after common muscle injuries.