Associate Professor The Chinese University of Hong Kong (CUHK) Hong Kong SAR, Hong Kong
Abstract: Tendinopathy, a painful condition arising from tendon overuse and aging, currently lacks effective treatments. This study explores the efficacy of adipose-derived stromal cells (ADSCs) and their secretome—comprising extracellular vesicles and soluble factors—on tendon healing in a rat model of degenerative tendinopathy. We aimed to optimize the dosage and injection frequency of both ADSCs and their secretome, examining their effects in rat tendons, and in tendon-derived stem/progenitor cells (TDSCs) isolated from healthy tendons (nTDSCs) and tendinopathic tendons (pTDSCs) of patients. ADSCs and their secretome were prepared by Rohto Advanced Research Hong Kong Ltd. nTDSCs and pTDSCs were treated with ADSCs or their secretome, with or without IL-1β stimulation, and the mRNA expression of inflammatory markers, matrix remodeling markers, and lineage differentiation markers was assessed using qRT-PCR. The effect of secretome on cell viability and migration was evaluated through Alamar Blue assays and scratch wound healing assays. In the rat model, animals received various doses of ADSCs and secretome at different frequencies following collagenase injection. Tendon samples were collected for histological, immunohistochemical, and mRNA analysis at specified intervals. Results indicated that ADSC secretome significantly enhanced the viability and migration of inflammatory nTDSCs and pTDSCs, counteracting the effects of IL-1β on the expression of inflammatory cytokines, matrix remodeling enzymes, and multilineage markers, with the secretome exhibiting superior efficacy in suppressing inflammation, matrix-degradation and promoting tenogenesis. High doses of ADSCs and a single equivalent dose of secretome exhibited comparable benefits in tendon repair over time, while multiple secretome injections did not provide additional advantages. Both treatments effectively suppressed inflammatory cytokines and matrix-degrading enzymes, promoting tenocyte marker expression. The similar in vivo effects of ADSCs and their secretome, coupled with superior in vitro results of the secretome, suggest that it is a promising cell-free alternative for treating tendinopathy.
Funding Source: This project was supported by Innovation and Technology Commission, HKSAR, China, with half of the funding provided by Rohto Advanced Research Hong Kong Ltd. (ARHK) (PRP/007/22FX).
