Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury

Abstract

Recently, adipose tissue-derived stem cells (ASCs) were emerged as an alternative, abundant, and easily accessible source of stem cell therapy. Previous studies revealed losartan (an angiotensin II type I receptor blocker) treatment promoted the healing of skeletal muscle by attenuation of the TGF-β signaling pathway, which inhibits muscle differentiation. Therefore, we hypothesized that a combined therapy using ASCs and losartan might dramatically improve the muscle remodeling after muscle injury. To determine the combined effect of losartan with ASC transplantation, we created a muscle laceration mouse model. EGFP-labeled ASCs were locally transplanted to the injured gastrocnemius muscle after muscle laceration. The dramatic muscle regeneration and the remarkably inhibited muscular fibrosis were observed by combined treatment. Transplanted ASCs fused with the injured or differentiating myofibers. Myotube formation was also enhanced by ASC + satellite coculture and losartan treatment. Thus, the present study indicated that ASC transplantation effect for skeletal muscle injury can be dramatically improved by losartan treatment inducing better niche.