Wharton's jelly mesenchymal stem cell-derived small extracellular vesicles as natural nanoparticles to attenuate cartilage injury via microRNA regulation

The main strategy of tissue repair and regeneration focuses on the application of mesenchymal stem cells and cell-based nanoparticles, but there are still multiple challenges that may have negative impacts on human safety and therapeutic efficacy. Cell-free nanotechnology can effectively overcome these obstacles and limitations. Mesenchymal stem cell (MSC)-derived natural small extracellular vesicles (sEVs) represent ideal nano-therapeutics due to their low immunogenicity and lack of tumorigenicity. Here, sEVs harvested from Wharton's jelly mesenchymal stem cells (WJMSCs) were identified. In vitro results showed that WJMSC-sEVs efficiently entered chondrocytes in the osteoarthritis (OA) model, further promoted chondrocyte migration and prolifera-tion and modulated immune reactivity. In vivo, WJMSC-sEVs notably promoted chondrogenesis, which was consistent with the effect of WJMSCs. RNA sequencing results revealed that sEV-microRNA-regulated biocircuits can significantly contribute to the treatment of OA, such as by promoting the activation of the calcium signaling pathway, ECM-receptor interaction pathway and NOTCH signaling pathway. In particular, let-7e-5p, which is found in WJMSC-sEVs, was shown to be a potential core molecule for promoting cartilage regeneration by regulating the levels of STAT3 and IGF1R. Our findings suggest that WJMSC-sEV-induced chondrogenesis is a promising innovative and feasible cell-free nanotherapy for OA treatment.

Automated summary

The main strategy of tissue repair and regeneration involves the application of mesenchymal stem cells and cell-based nanoparticles, but there are challenges that may impact safety and efficacy. Cell-free nanotechnology can overcome these obstacles. This study focuses on using sEVs derived from Wharton's jelly mesenchymal stem cells for chondrogenesis and modulation of immune reactivity in the treatment of osteoarthritis. The results show promising outcomes and the potential of sEVs as a cell-free nanotherapy for OA treatment.