In the muscle tissue exist different cell populations that are able to participate in muscle regeneration. The presence of distinct muscle progenitor subtypes with different cellular plasticity raises the question of whether and how these cells participate to the muscle ontogeny. The regenerative capacity of skeletal muscle is due to a combination of factors which leads to the activation of the satellite cell (SC) pool. Recently, several studies documented the role of interstitial muscle cells during muscle regeneration. In this study we analyzed the Lin−(CD31−CD45−TER119−) human interstitial muscle cells isolated from healthy and DMD muscle biopsies. Among human interstitial muscle cells we found cell population expressing CD56 (NCAM), CXCR4, CD29 (β-1 Integrin) satellite markers and cells positive for CD34 and PDGFalpha (FAP) with adipogenic and fibrogenic potentials and cells expressing CD44, CD29, CD73 antigens with mesenchymal (MSC) potential. The number of satellite and mesenchymal interstitial cells was reduced in older DMD muscle with a loss of their clonogenicity and myogenic potential. Contrarily, we observed an age-dependent increase in DMD adipogenic interstitial cells together with an overexpression of PDGFRα confirmed by WB analysis. In vivo studies of intra-muscular transplantation of the selected sorted human interstitial subpopulations in scid/mdx mice (dystrophic animal model which allow the transplantation of human cells) confirmed the failure of the muscle regenerative capacities of satellite and MSC cells isolated from DMD muscle biopsies with an increased in vivo adipogenesis. In light of all these results, we confirmed the exhaustion of myogenic progenitors in dystrophic DMD muscle tissues providing insights of DMD pathology.
|Titolo:||Impact of Muscular Dystrophy on the Regenerative Properties of interstitial Muscle Cells|
|Data di pubblicazione:||25-mar-2019|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Citazione:||Impact of Muscular Dystrophy on the Regenerative Properties of interstitial Muscle Cells / M.L.C. Belicchi, M.A. Meregalli, S.A. Erratico, A. Cattaneo, C. Villa, A. Farini, L. Porretti, Y. Torrente. ((Intervento presentato al convegno Myology tenutosi a Bordeaux nel 2019.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|