CD146 + cell engraftment improves vascularization, and impact tissue remodelling in dystrophic skeletal muscle of mdx mice

Abstract

CD146 + cells have been described as myogenic progenitors residing in the interstitial space of skeletal muscle in both mice and humans. Previous studies demonstrated that intramuscular transplantation of CD146 + cells can enhance regeneration of injured or immobilized skeletal muscle. Moreover, our earlier work showed that a dystrophic environment alters CD146 + cell characteristics, reducing their myogenic potential while promoting adipogenic and fibrogenic differentiation. In this study, we investigated the role of CD146 + cells during muscle development and assessed their regenerative capacity following engraftment in dystrophic muscle of mdx mice. We found that CD146 + cells are present in mouse embryos at embryonic days 12 and 15, predominantly within the developing heart, somites, and limb buds. During adult muscle regeneration, the number of CD146 + cells increased and peaked at days 7 and 14 post BaCl 2 -induced injury in muscles of wild type but not mdx mice. Consistently, qPCR analysis revealed disrupted expression patterns of factors associated with pericytes, fibro-adipogenic progenitors, and myogenic progenitors in regenerating mdx mouse muscles compared to wild type. Finally, transplantation of CD146+/GFP+ cells obtained from healthy animals into mdx mouse skeletal muscles subjected to either BaCl₂-induced injury or treadmill-induced damage resulted in model-specific improvements: reduced collagen deposition following acute injury and decreased adipose tissue infiltration following exercise-induced damage, both accompanied by enhanced vascularization. Together, our findings indicate that CD146 + cells contribute to muscle remodelling and vascularization and highlight their context-dependent regenerative potential in dystrophic muscles.