Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic

人胎盘外泌体(pExo)作为骨关节炎疾病潜在改良治疗药物的表征

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作者:Chenfei Huang, Yuechao Zhao, Shengchen Lin, Lin Li, Xuan Guo, Sebastian Yumiseba, Jeng-Dar Yang, Robert Hariri, Qian Ye, Shuyang He, Adrian Kilcoyne

Conclusions

Our study demonstrates that pExo has multiple potential therapeutic effects including symptom control and disease modifying characteristics. This may make it an attractive candidate for further development as an anti-OA therapeutic.

Methods

pExo was generated from full-term human placenta tissues by sequential centrifugation, purification, and sterile filtration. Upon analysis of particle size, cytokine composition, and exosome marker expression, pExo was further tested in cell-based assays to examine its effects on human chondrocytes. In vivo therapeutic efficacies were evaluated in a medial meniscal tear/medial collateral ligament tear (MCLT + MMT) rat model, in which animals received pExo injections intraarticularly and weight bearing tests during in-life stage while histopathology and immunohistochemistry were performed as terminal endpoints.

Objective

Human placenta-derived exosomes (pExo) were generated, characterized, and evaluated as a therapeutic candidate for the treatment of osteoarthritis (OA).

Results

pExo displayed typical particle size, expressed maker proteins of exosome, and contained proteins with pro-proliferative, pro-anabolic, anti-catabolic, or anti-inflammatory activities. In vitro, pExo promoted chondrocyte migration and proliferation dose-dependently, which may involve its activation of cell growth-related signaling pathways. Expression of inflammatory and catabolic genes induced in a cellular OA model was significantly suppressed by pExo. In the rat OA model, pExo alleviated pain burden, restored cartilage degeneration, and downregulated expressions of pro-inflammatory, catabolic, or apoptotic proteins in a dose-dependent manner. Conclusions: Our study demonstrates that pExo has multiple potential therapeutic effects including symptom control and disease modifying characteristics. This may make it an attractive candidate for further development as an anti-OA therapeutic.

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