Abstract

Background:Adipose stem cell–derived exosomes (ASC-Exos) are reported to effectively prevent muscle atrophy and degeneration of torn rat rotator cuff, but their influence on human samples and their potential mechanism are still unclear.Purpose:We aimed to investigate the effects of ASC-Exos on the metabolic activities of torn human rotator cuff tendons and explore the potential mechanism behind it.Study Design:Controlled laboratory study.Methods:Diseased supraspinatus tendons were harvested from 15 patients with a mean ± SD age of 65.8 ± 3.2 years who underwent reverse shoulder arthroplasty for chronic rotator cuff tears associated with glenohumeral pathological changes. Each tendon was dissected into 3 × 4 × 4–mm explants: the ones derived from the same tendon were placed into 12-well plates and cultured in complete culture media (control) or in complete culture media supplemented with ASC-Exos for 72 hours. Afterward, the concentrations of cytokines secreted into the culture media—including interleukin 1β (IL-1β), IL-6, IL-8, and matrix metalloproteinase 9 (MMP-9)—were measured using enzyme-linked immunosorbent assay (ELISA). Tendons were stained with hematoxylin and eosin and immunohistochemistry (type I and III collagens) for histological analyses. Moreover, the expression of anabolic genes (TIMP-1 and TIMP-3; type I and III collagen encoding) and catabolic genes (MMP-9 and MMP-13) in tendons were measured using real-time quantitative polymerase chain reaction. Phosphorylated AMPKα and Wnt/β-catenin pathways were assayed by western blotting to explore the potential mechanism of action of ASC-Exos.Results:Secretion of proinflammatory cytokines, including IL-1β, IL-6, and MMP-9, was significantly reduced in the ASC-Exos group as compared with the control group. Supraspinatus tendons in the ASC-Exos group exhibited superior histological properties, as demonstrated by higher tendon maturing scores and more type I collagen content, but there was no significant diffe