Sertoli cells (SeC), which are crucial for germinal cell development, have demonstrated trophic and immunomodulatory effects in numerous experimental setting.1 A single injection of microencapsulated SeC into the peritoneal cavity of mdx mice, an experimental model of Duchenne muscular dystrophy (DMD), results into recovery of muscle architecture and performance in the absence of any pharmacological immunosuppression, opening to new perspectives for DMD treatment.2 Besides restraining muscle inflammation, treatment of mdx mice with microencapsulated SeC induced at the sarcolemma of myofibers the expression of the dystrophin paralogue, utrophin, thus conferring an additional advantage to dystrophic muscles.2 However, the direct effects of SeC on myoblasts/myotubes themselves and on myotubes of higher mammals have not been investigated yet. C2C12 myotubes treated with TNFα/IFNγ or cultured in PBS (phosphate buffered saline) to mimic atrophying conditions show reduced levels of myosin heavy chain (MyHC), and we found that SeC protect against loss of MyHC in both conditions in a dose-dependent manner, high numbers of SeC being the most efficacious. Moreover, we demonstrated that, as for mdx myotubes/myofibers,2 SeC are able to induce utrophin expression in myotubes from GRMD (golden retriever muscular dystrophy) dogs and dystrophic humans. Our data further support the use of microencapsulated SeC for treatment of DMD patients. References: 1. Mital et al. (2010) Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible. Reproduction 139: 495-504. 2. Chiappalupi et al. (2016) Intraperitoneal injection of microencapsulated Sertoli cells restores muscle morphology and performance in dystrophic mice. Biomaterials 75: 313-26.
Sertoli cells protect C2C12 myotubes against atrophy and induce utrophin expression in canine and human dystrophic myotubes.
Salvadori L.;Chiappalupi S.;Luca G.;Sagheddu R.;Riuzzi F.;Mancuso F.;Calvitti M.;Arato I.;Calafiore R.;Donato R.;Sorci G.
2017
Abstract
Sertoli cells (SeC), which are crucial for germinal cell development, have demonstrated trophic and immunomodulatory effects in numerous experimental setting.1 A single injection of microencapsulated SeC into the peritoneal cavity of mdx mice, an experimental model of Duchenne muscular dystrophy (DMD), results into recovery of muscle architecture and performance in the absence of any pharmacological immunosuppression, opening to new perspectives for DMD treatment.2 Besides restraining muscle inflammation, treatment of mdx mice with microencapsulated SeC induced at the sarcolemma of myofibers the expression of the dystrophin paralogue, utrophin, thus conferring an additional advantage to dystrophic muscles.2 However, the direct effects of SeC on myoblasts/myotubes themselves and on myotubes of higher mammals have not been investigated yet. C2C12 myotubes treated with TNFα/IFNγ or cultured in PBS (phosphate buffered saline) to mimic atrophying conditions show reduced levels of myosin heavy chain (MyHC), and we found that SeC protect against loss of MyHC in both conditions in a dose-dependent manner, high numbers of SeC being the most efficacious. Moreover, we demonstrated that, as for mdx myotubes/myofibers,2 SeC are able to induce utrophin expression in myotubes from GRMD (golden retriever muscular dystrophy) dogs and dystrophic humans. Our data further support the use of microencapsulated SeC for treatment of DMD patients. References: 1. Mital et al. (2010) Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible. Reproduction 139: 495-504. 2. Chiappalupi et al. (2016) Intraperitoneal injection of microencapsulated Sertoli cells restores muscle morphology and performance in dystrophic mice. Biomaterials 75: 313-26.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
