Chondrocyte-derived apoptotic vesicles enhance stem cell biological function for the treatment of cartilage injury

Transplanting chondrocytes has been extensively explored as a possible treatment option for conditions linked to cartilage degradation. There are, however, a number of disadvantages and possible treatment processes that have not been well investigated. Research indicates that while treating cartilage damage, transplanted chondrocytes go through apoptosis and produce apoptotic vesicles (apoVs). It is still unknown what apoVs are like, how they work, and whether or not they have positive therapeutic benefits. In order to achieve regenerative regeneration following cartilage damage, we developed a cell-free therapeutic approach that combines decellularized cartilage extracellular matrix (DCECM) scaffolds with chondrocyte-derived apoVs (Cho-apoVs). Specifically, we characterised Cho-apoVs at the molecular level and discovered that they were enriched with cartilage-regenerating functional proteins. Cho-apoVs have been shown in vitro to promote phagocytic transcriptional reprogramming in bone marrow mesenchymal stem cells (BMSCs) and improve their chondrogenesis, migration, and proliferation capacities. Moreover, we discovered that miR-16-5p was a miRNA that was highly abundant in Cho-apoVs using high-throughput sequencing. Through activating the TGF-β signalling pathway, miR-16-5p has been demonstrated to speed regenerative healing of cartilage damage and increase chondrogenic differentiation of BMSCs. The ability of DCECM scaffolds loaded with Cho-apoVs to stimulate cartilage regeneration was validated by the outcomes of the rat knee osteochondral defect repair model. In conclusion, DCECM scaffolds loaded with Cho-apoVs appear to be a clinically viable cell-free alternative for the regenerative repair therapy of cartilage injury. Cho-apoVs also demonstrate good therapeutic potential capable of safeguarding cartilage homeostasis and regeneration.