By producing nutrients and immunomodulatory factors Sertoli cells (SCs) are able to modulate the immune responses and inflammation when implanted in several experimental models of diseases. Most myopathies, including Duchenne muscular dystrophy (DMD) are characterized by a progressive muscle degeneration associated with chronic inflammation, leading to muscle necrosis and fibrosis. The only intervention so far able to improve survival of DMD patients is the treatment with antiinflammatory steroids, despite their limited efficacy and undesired side effects. We transplanted SCs encapsulated into highly biocompatible microcapsules into the peritoneal cavity of the DMD mouse model, mdx. Three weeks after transplantation muscles from SC-treated mice compared with muscles from mock-treated mice showed: i) dramatically reduced numbers of inflammatory cells; ii) a significant decrease in fibrous and adipose tissue infiltration; and, iii) markedly decreased numbers of necrotic and regenerating myofibers, and increased numbers of regenerated myofibers. Finally, SC-treated but not mock-treated mdx mice showed recovery of muscle performance and a comparable resistance to exercise-induced muscle damage to that of untreated wild-type mice. Transplantation of microencapsulated SCs may represent a powerful means to reduce muscle inflammation, and promote muscle regeneration and growth in subjects affected from DMD and, potentially, muscular diseases characterized by chronic inflammation.
Transplantation of microencapsulated Sertoli cells: a new potential antiinflammatory approach to Duchenne muscular dystrophy (DMD).
Chiappalupi S.;SORCI, Guglielmo;LUCA, Giovanni;MANCUSO, FRANCESCA;CALVITTI, Mario;ARATO, IVA;Falabella G.;CALAFIORE, Riccardo;DONATO, Rosario Francesco
2012
Abstract
By producing nutrients and immunomodulatory factors Sertoli cells (SCs) are able to modulate the immune responses and inflammation when implanted in several experimental models of diseases. Most myopathies, including Duchenne muscular dystrophy (DMD) are characterized by a progressive muscle degeneration associated with chronic inflammation, leading to muscle necrosis and fibrosis. The only intervention so far able to improve survival of DMD patients is the treatment with antiinflammatory steroids, despite their limited efficacy and undesired side effects. We transplanted SCs encapsulated into highly biocompatible microcapsules into the peritoneal cavity of the DMD mouse model, mdx. Three weeks after transplantation muscles from SC-treated mice compared with muscles from mock-treated mice showed: i) dramatically reduced numbers of inflammatory cells; ii) a significant decrease in fibrous and adipose tissue infiltration; and, iii) markedly decreased numbers of necrotic and regenerating myofibers, and increased numbers of regenerated myofibers. Finally, SC-treated but not mock-treated mdx mice showed recovery of muscle performance and a comparable resistance to exercise-induced muscle damage to that of untreated wild-type mice. Transplantation of microencapsulated SCs may represent a powerful means to reduce muscle inflammation, and promote muscle regeneration and growth in subjects affected from DMD and, potentially, muscular diseases characterized by chronic inflammation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.