Testicular Sertoli cells (SeC) physiologically secrete several trophic and immunomodulatory factors thanks to which they have been used in numerous experimental settings and pre-clinical studies, including treatment of diabetes and neurodegenerative disorders [1,2]. A single intraperitoneal (i.p.) injection of microencapsulated porcine SeC (SeC-MC) resulted in recovery of muscle morphology and performance in mdx mice, without any pharmacological immunosuppression [3]. This effect was dependent on the release by SeC-MC of antiinflammatory factors and heregulin beta 1, which from the peritoneal cavity through the circulation reach muscles where they reduce inflammation and induce the expression of the dystrophin paralogue, utrophin at the sarcolemma, respectively [3]. We found that lower doses of SeC-MC than those previously used [3] induced significant reduction of inflammation (MAC3 expression) and percentages of necrotic myofibers, and increased expression of utrophin in muscles of mdx mice. Also, transmission electron microscopy analysis showed that SeC inside freshly-prepared microcapsules retained a good morphology of nucleus, cell wall and cytoplasmic organelles. Moreover, SeC protected myotubes against atrophy [i.e., loss of myosin heavy chain (MyHC), reduction of myotube diameters, and increased expression of the atrogenes¸ atrogin-1 (Fbxo32) and Murf-1 (Trim63)] induced by treatment with the corticosteroid, dexamethasone (Dex), in a dose-dependent manner in vitro. Accordingly, SeC-MC protected muscles against atrophy in an experimental model of cancer-induced cachexia (i.e., LLC tumor-bearing mice), as evaluated by the expression levels of Fbxo32 and Trim63. Interestingly, treatment with SeC-MC did not affect tumor growth in vivo, supporting the concept of an immunomodulatory rather than immunosuppressive effect of SeC. Altogether, our data suggest a role of SeC in counteracting loss of muscle mass in different experimental conditions, and further support the use of i.p. injection of SeC-MC as a potential treatment of DMD patients.
Novel data support the use of microencapsulated Sertoli cells as a potential treatment of DMD patients.
Salvadori L.;Chiappalupi S.;Luca G.;Riuzzi F.;Mancuso F.;Calvitti M.;Arato I.;Calafiore R.;Donato R.;Sorci G.
2018
Abstract
Testicular Sertoli cells (SeC) physiologically secrete several trophic and immunomodulatory factors thanks to which they have been used in numerous experimental settings and pre-clinical studies, including treatment of diabetes and neurodegenerative disorders [1,2]. A single intraperitoneal (i.p.) injection of microencapsulated porcine SeC (SeC-MC) resulted in recovery of muscle morphology and performance in mdx mice, without any pharmacological immunosuppression [3]. This effect was dependent on the release by SeC-MC of antiinflammatory factors and heregulin beta 1, which from the peritoneal cavity through the circulation reach muscles where they reduce inflammation and induce the expression of the dystrophin paralogue, utrophin at the sarcolemma, respectively [3]. We found that lower doses of SeC-MC than those previously used [3] induced significant reduction of inflammation (MAC3 expression) and percentages of necrotic myofibers, and increased expression of utrophin in muscles of mdx mice. Also, transmission electron microscopy analysis showed that SeC inside freshly-prepared microcapsules retained a good morphology of nucleus, cell wall and cytoplasmic organelles. Moreover, SeC protected myotubes against atrophy [i.e., loss of myosin heavy chain (MyHC), reduction of myotube diameters, and increased expression of the atrogenes¸ atrogin-1 (Fbxo32) and Murf-1 (Trim63)] induced by treatment with the corticosteroid, dexamethasone (Dex), in a dose-dependent manner in vitro. Accordingly, SeC-MC protected muscles against atrophy in an experimental model of cancer-induced cachexia (i.e., LLC tumor-bearing mice), as evaluated by the expression levels of Fbxo32 and Trim63. Interestingly, treatment with SeC-MC did not affect tumor growth in vivo, supporting the concept of an immunomodulatory rather than immunosuppressive effect of SeC. Altogether, our data suggest a role of SeC in counteracting loss of muscle mass in different experimental conditions, and further support the use of i.p. injection of SeC-MC as a potential treatment of DMD patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
