Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

By Shi‐Cong Tao, Ting Yuan, Yue-Lei Zhang, Wenjing Yin, Shang-Chun Guo, Chang-Qing Zhang. Theranostics, 2017

648 citations recorded by the source corpus.

OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p. Exosomes derived from SMSCs or SMSC-140s (SMSC-Exos or SMSC-140-Exos) were isolated and identified. Proliferation, migration and ECM secretion were measured in vitro and compared between groups. The mechanism involving alternative Wnt signalling and activation of Yes-associated protein (YAP) was investigated using lentivirus, oligonucleotides or chemical drugs. The preventative effect of exosomes in vivo was measured using Safranin-O and Fast green staining and immunohistochemical staining. RESULTS: Wnt5a and Wnt5b carried by exosomes activated YAP via the alternative Wnt signalling pathway and enhanced proliferation and migration of chondrocytes with the side-effect of significantly decreasing ECM secretion. Highly-expressed miR-140-5p blocked this side-effect via RalA. SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion in vitro, while in vivo, SMSC-140-Exos successfully prevented OA in a rat model. CONCLUSIONS: These findings highlight the promising potential of SMSC-140-Exos in preventing OA. We first found a potential source of exosomes and studied their merits and shortcomings. Based on our understanding of the molecular mechanism, we overcame the shortcomings by modifying the exosomes. Such exosomes derived from modified cells hold potential as future therapeutic strategies.

Subfields: Molecular Biology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/7dde5a8ba1e1d3b7ed679730ede40056409bda56

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Citations in the corpus

Clinical applications of stem cell-derived exosomes (2024, background): “83 Meanwhile, Wang et al. used TGF-β 1 to stimulate MSCs, and the resultant exosomal miR-135b increased chondrocyte proliferation by regulating speci ﬁ city protein-1.”
MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. (2018, result): “Unlike a previous report where only exosomes from miR-140-5p overexpressing synovial MSCs could enhance matrix synthesis of chondrocytes [49], we showed here that native MSC exosomes could enhance matrix synthesis of chondrocytes without the need for genetic manipulation.”