Intraperitoneal transplantation of microencapsulated Sertoli cells counteracts muscle inflammation and rescues muscle performance in mdx mice.

Duchenne muscular dystrophy (DMD), a progressive muscle degenerative disease associated with chronic inflammation, necrosis and fibrosis, is currently treated with antiinflammatory steroids, despite their limited efficacy and undesired side effects. Testicular Sertoli cells (SCs) have been successfully implanted to treat many experimental diseases due to their ability to secrete trophic, antiinflammatory and immunomodulatory molecules [1]. We transplanted microencapsulated SCs, within highly biocompatible microcapsules [2] into the peritoneal cavity of mdx mice, an animal model of DMD. Skeletal muscles from SC-treated mdx mice, compared with muscles from mock-treated mice displayed reduced necrosis, improved regeneration and depletion of infiltrated inflammatory cells, with a significant reduction of the number of macrophages already one week after transplantation. Serum IFN-gamma, a strong inducer of pro-inflammatory macrophages elevated in mdx mice was significantly reduced in SC-treated mice. Three weeks after transplantation SC-treated, but not mock-treated mdx mice showed recovery of muscle performance in treadmill running tests, and a comparable resistance to exercise-induced muscle damage to that of untreated wild-type mice. Unexpectedly, muscles from SC-treated mdx mice showed an increased expression of the dystrophin-related gene, utrophin (Utrn) which might contribute to the recovery of muscle homeostasis. Similarly to mdx mice, transplantation of SCs in an experimental model of autoimmune myositis resulted in the recovery of limb muscle mass and dramatic reduction of necrosis in diaphragm. Our results suggest that i.p. transplantation of microencapsulated SCs might represent a powerful means to reduce muscle inflammation and create a more suitable microenvironment for muscle regeneration and the recovery of muscle performance in animals and, possibly patients affected from DMD or inflammatory myopathies. [1] Mital et al. Reproduction 139(2010): 495-504; [2] Luca et al. Tissue Eng 13(2007): 641-8.