PhD student The Chinese University of Hong Kong (CUHK), China (People's Republic)
Abstract: Tendinopathy, a common musculoskeletal disorder, is a chronic disease of an unknown etiology and associated with inflammation. Currently, conservative and surgical treatments often prove to be insufficient for the complete resolution of symptoms, with some patients unfortunately needing to undergo surgery at a later stage. Exosomes are nano-sized extracellular vesicles (30-150 nm in diameter) secreted by various cell types, including mesenchymal stem cells (MSCs). These vesicles play a crucial role in intercellular communication by transferring bioactive molecules such as proteins, lipids, and nucleic acids (mRNAs and miRNAs) between cells. Exosomes derived under acidic preconditioned tendon-derived stem cells (TDSCs) may carry a distinct cargo of proteins, lipids, and genetic material that is specifically tailored to promote tissue repair. Therefore, the objective of this study was to investigate the pro-tenogenic bioactivity of low pH exosomes on TDSCs, and to develop GelMA-loaded exosomes for the repair of Achilles tendinopathy.Our results demonstrated that: Exosomes derived from acidic conditions (pH 5.0) enhanced the proliferation and migration of rATSCs. At day 3, rATSCs treated with pH 5 exosomes exhibited decreased expression of pro-inflammatory cytokines and increased expression of the anti-inflammatory cytokine IL-10. At days 6 and 12, rATSCs treated with pH 5 exosomes demonstrated increased expression of tenogenic markers. Compared to pH 7.35 exosomes, pH 5 exosome loading implantation in rat Achilles tendon resulted in significantly enhanced histological and functional tendon repair at week 4. Our study suggested that low pH-preconditioned tendon-derived stem cell exosomes exhibit potent tenogenic bioactivity in vitro and enhance tendon repair in vivo in rat Achilles tendinopathy. Further optimization of exosomes will be necessary to improve its tendon regeneration efficacy. Additionally, investigations into the underlying mechanism of action will also be needed to justify its potential clinical translation for tendon repair.
