Platelet-derived mitochondria attenuate muscle atrophy following rotator cuff tears in a rat model.

Abstract

Rotator cuff tears (RCTs) often result in muscle atrophy, compromising surgical outcomes and recovery. Mitochondrial dysfunction is implicated in this process, suggesting potential for mitochondria-based therapies. This study aimed to investigate the effects of platelet-derived mitochondria (Plt-Mito) administration into the supraspinatus muscle (SSP) following RCTs. Seventy-two male Sprague-Dawley rats were allocated into 3 distinct groups: (1) a sham surgery group, (2) a group with RCTs treated with Plt-Mito, and (3) a group with RCTs treated with phosphate-buffered saline. Treatments were administered every 2 weeks. After 12 weeks, the SSPs were analyzed for wet muscle weight ratio, muscle fiber cross-sectional area, fibrosis, antioxidant activity, mitochondrial markers, capillary density, and mitochondrial structure. Plt-Mito successfully incorporated into SSP, maintaining functional integrity. Compared to the phosphate-buffered saline group, Plt-Mito treatment significantly preserved wet muscle weight, increased mean muscle fiber cross-sectional area, promoted muscle regeneration, reduced fibrosis, enhanced antioxidant activity (increased superoxide dismutase activity and decreased malondialdehyde activity), improved muscle vascularity (increased platelet endothelial cell adhesion molecule-1 and α-smooth muscle actin), increased expression of mitochondrial markers (C oxidase subunit IV and uncoupling protein 1) and maintained mitochondrial density and structure. Our findings demonstrated Plt-Mito administration effectively halted muscle atrophy and fibrosis, while attenuating mitochondrial damage and dysfunction following RCTs.