Platelet-rich plasma-derived exosomes have the novel ability to alleviate insertional Achilles tendinopathy by promoting tenogenesis in tendon stem/progenitor cells

Insertional Achilles tendinopathy (IAT) is a highly prevalent overuse injury affecting the foot and ankle in clinical settings. Currently, the primary management approach is conservative treatment. Platelet-rich plasma-derived exosomes (PRP-Exos) effectively preserve essential growth factors and other vital components inherent in PRP, thereby optimizing overall treatment outcomes. Furthermore, the standardized microinjection technique for PRP-Exos significantly enhances the treatment experience for patients. In this study, PRP-Exos were isolated from SD rats, and their effects on proliferation, migration, differentiation, apoptosis and other physiological processes in tendon-derived stem cells (TDSCs) in an IL-1β-induced inflammatory state were investigated in vitro. In this context, we conducted a thorough investigation of the impact of PRP-Exos on the tendinogenic differentiation of TDSCs under inflammatory conditions and explored the underlying mechanisms through cellular RNA sequencing. In vivo, the therapeutic effects of PRP-Exos on IAT at different times after treatment were evaluated comprehensively via histological analysis, behavioral tests and biomechanical tests. The results showed that PRP-Exos significantly increased the proliferation and migration of TDSCs in an inflammatory state in vitro and promoted their differentiation into tendon cells. Animal experiments confirmed that the histology, biomechanical performance and behavior of the animals in the PRP-Exos group were significantly normalized. This work demonstrated that the topical use of PRP-Exos at the insertion site of the Achilles tendon is an effective strategy for regulating proliferation and tendinogenic differentiation and represents a novel treatment approach for IAT.