Decellularized extracellular matrix restores Fibronectin/Integrin β1 balance through extracellular vesicles to rejuvenate chondrocytes and alleviate osteoarthritis progression.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Osteoarthritis (OA) is a prevalent degenerative joint disease driven largely by chondrocyte senescence. Extracellular vesicle (EV)-based therapies have emerged as a promising strategy; however, the extensive stem-cell expansion required to obtain therapeutic EV doses unavoidably erodes their potency. Objectives Leveraging our prior finding that decellularized extracellular matrix (dECM) rejuvenates stem cells during in vitro expansion, we further investigate whether dECM could resolve the current bottleneck in EV therapy by preserving therapeutic efficacy even in late-passage cells. Methods Human adipose-derived stromal cells (hADSCs) were expanded to passage 15 on either tissue culture plastic (TCP) or dECM, and their EVs were isolated. We first interrogated the capacity of dECM-primed EVs to counteract chondrocyte senescence and ER stress in vitro, then validated their therapeutic impact in a rat OA model. Mechanistic insight was pursued through proteomic profiling, followed by loss- and gain-of-function studies using pharmacologic inhibitors and targeted knockdown. Results Late-passage EVs generated under dECM (dECM-P15-EVs) surpassed those under TCP (TCP-P15-EVs) in alleviating chondrocyte senescence and ER stress. In vivo, dECM-P15-EVs attenuated cartilage degradation more effectively than their conventionally cultured counterparts. Proteomics revealed dECM-P1

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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