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人脐带间充质干细胞来源的外泌体对大鼠骨关节炎模型的作用。

Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models.

机构信息

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, People's Republic of China.

Department of R&D, Oricell Therapeutics, Shanghai, 201203, People's Republic of China.

出版信息

Stem Cells Transl Med. 2024 Aug 16;13(8):803-811. doi: 10.1093/stcltm/szae031.

Abstract

Mesenchymal stem cells (MSCs) offer great potential for treatment of osteoarthritis (OA) by promoting articular cartilage regeneration via paracrine secretion of exosomes; however, the underlying mechanisms are not fully understood. This study aimed to explore the therapeutic effects of exosomes secreted by human umbilical cord-derived MSCs (hUC-MSCs) in rat models of OA and reveal the underlying mechanisms. UC-MSCs and UC-MSC-exosomes were prepared and identified by transmission electron microscopy and flow cytometry. IL-1β-induced OA chondrocytes and the operation and collagenase-induced OA rat models were established. The results of micro-computed tomography, histology, and immunohistochemistry showed that UC-MSC-exosomes promoted cartilage regeneration in OA rats. ELISA results showed that the levels of synovial fluid cytokines, TNF-α, IL-1β, and IL-6, were lower in exosome therapy group than control group in both OA rat models. Exosome treatment significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1β, and upregulated collagen II expression. These findings suggest that hUC-MSC-exosomes offer a promising option for the therapy for OA.

摘要

间充质干细胞 (MSCs) 通过旁分泌外泌体促进关节软骨再生,为治疗骨关节炎 (OA) 提供了巨大的潜力;然而,其潜在机制尚不完全清楚。本研究旨在探讨人脐带间充质干细胞 (hUC-MSCs) 分泌的外泌体在 OA 大鼠模型中的治疗作用,并揭示其潜在机制。通过透射电子显微镜和流式细胞术对 UC-MSCs 和 UC-MSC-外泌体进行了制备和鉴定。建立了 IL-1β诱导的 OA 软骨细胞和手术及胶原酶诱导的 OA 大鼠模型。结果显示,UC-MSC-外泌体促进了 OA 大鼠的软骨再生。ELISA 结果显示,在两种 OA 大鼠模型中,外泌体治疗组关节滑液细胞因子 TNF-α、IL-1β和 IL-6 的水平均低于对照组。外泌体治疗显著下调了 IL-1β刺激的软骨细胞中 MMP-13 和 ADAMTS-5 的表达,并上调了胶原 II 的表达。这些发现表明 hUC-MSC-外泌体为 OA 的治疗提供了一种有前途的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8212/11328936/1d9ffd1853fc/szae031_fig5.jpg

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