Enhancing Myoblast Proliferation by Using Myogenic Factors: A Promising Approach for Improving Fiber Regeneration in Sport Medicine and Skeletal Muscle Diseases

Macrophages drive muscle regeneration and repair by removing necrotic material and producing key signaling molecules. The array of cytokines/growth factors produced by macrophages and myogenic cells stimulates the proliferation, migration and differentiation of satellite cells. Although the details of such processes are only partially understood, it is known that the administration of purified growth factors can improve the final outcome after traumatic muscle injuries. Also, such approach has proved to be beneficial in myoblast transplantation experiments in animal models. The translation of such procedures into therapeutic protocols is, however, hampered by high costs and the somewhat oversimplified biochemical input compared to the physiological signal network. We have previously reported that peritoneal macrophages could secrete factors capable of increasing the myoblast/myotube yield in cultures of primary rat myoblasts. Recently, we observed that a macrophage cell line could be stimulated to produce a conditioned medium that specifically enhances the proliferation of cultured neonatal primary myoblasts from mouse, rat, chicken, and human fetal myoblasts. The factors did not inhibit differentiation and led to a striking increase in the rate of contractile myotube formation. The factors could also enhance muscle regenerative processes in vivo, thereby suggesting a potential role as an economical and effective tool for the treatment of traumatic and disease-related muscle injuries. Further experiments in this direction and the biochemical characterization of the macrophage-produced myogenic factors are presently underway. The possibility to use the macrophage factors to improve the myoblast yield from diseased-muscle biopsies is also under investigation. Abbreviations: MCM: macrophage-conditioned medium.