Harnessing bi-exosome synergy alleviates osteoarthritis progression

Osteoarthritis (OA), with complicated pathogenesis, including chronic inflammation, anabolic suppression, cartilage degeneration, among other factors, leads to a lack of suitable treatments. Despite the promising effects of cell-based therapy in reducing clinical osteoarthritis severity, a single biological modality makes it hard to achieve comprehensive chondroprotective function. Herein, we propose a bi-exosome synergy strategy, which combines anti-inflammatory bone marrow mesenchymal stromal cell-derived exosomes (BMSC-Exo) and anti-catabolic cartilage progenitor cell-derived exosomes (CPC-Exo), to alleviate osteoarthritis progression. The BMSC/CPC-Exo were identified with distinct enrichment of miRNA contents, emphasizing macrophage and chondrocyte modulation, respectively. Compared to single-exosome treatment, the bi-exosome synergy remarkably postponed OA progression via simultaneously combating joint inflammatory and catabolic environment, in which the dominant pathways of miR-708-5p/NRP-1, miR-431/BRCA-1/PLK-1, and miR-7a-5p/NOTCH-3 were further confirmed. This work presents the tailoring of exosome compositions to modulate multitargeting, thereby creating a potential for OA treatment.