Delivery of a tissue derived extracellular matrix gel modulates early fibro-adipogenic cell behavior and improves recovery following both acute and chronic atrophy muscle injury

Abstract

In this study we examined the potential of muscle derived extracellular matrix (ECM) gel prepared from skeletal muscle as a treatment strategy for acute and chronic degenerative atrophy. We conducted experiments to evaluate the gel’s effectiveness in both a mouse hindlimb unloading (HU) model (disuse atrophy), and on a rabbit shoulder rotator cuff tear (RCT) model (diseased atrophy). In the HU mouse model, the gel enhanced denovo muscle regeneration (4000% higher in centralized nuclei myofiber density) and muscle mass (22% heavier) in the tibialis anterior muscle compared to PBS group. The transcriptomic and proteomic analysis using mouse tissues revealed that the gel elicited adult myogenesis programme. In the RCT rabbit model, the gel enhanced muscle mass (19% heavier), average myofiber cross-sectional area (29% larger), and lowered fatty infiltration (72% less fat) in the supraspinatus muscle compared to repair only. The transcriptomic and proteomic analysis using rabbit tissues revealed that the gel enhanced recovery through promoting a pro-myogenic muscle environment while lessening adipogenesis. The findings suggested that gel injection had a positive effect on the treatment of muscle atrophy and the therapeutic effect of the ECM gel was in part via its impact on fibro-adipogenic progenitor cell behavior, a mechanistic finding that could be exploited for even greater impact.