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

被引:17
作者
Yang, Huanfeng [1 ,2 ]
Zhou, Yiqin [3 ]
Ying, Bi [2 ]
Dong, Xuhui [2 ]
Qian, Qirong [3 ]
Gao, Shaorong [1 ,4 ,5 ]
机构
[1] Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Inst Regenerat Med,Shanghai East Hosp, Shanghai 200120, Peoples R China
[2] Oricell Therapeut, Dept R&D, Shanghai 201203, Peoples R China
[3] Naval Med Univ, Shanghai Changzheng Hosp, Dept Orthoped, Shanghai 200003, Peoples R China
[4] Tongji Univ, Shanghai Matern & Infant Hosp 1, Shanghai Inst Maternal Fetal Med & Gynecol Oncol, Clin & Translat Res Ctr,Shanghai Key Lab Maternal, Shanghai 201204, Peoples R China
[5] Tongji Univ, Frontier Sci Ctr Stem Cell Res, Shanghai 200092, Peoples R China
关键词
mesenchymal stem cells; exosomes; osteoarthritis; umbilical cord; regeneration; KNEE OSTEOARTHRITIS; CARTILAGE; PATHOGENESIS; INFLAMMATION; CYTOKINES; PATHWAY; IL-6;
D O I
10.1093/stcltm/szae031
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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-1 beta-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-alpha, IL-1 beta, 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-1 beta, and upregulated collagen II expression. These findings suggest that hUC-MSC-exosomes offer a promising option for the therapy for OA. Graphical AbstractExosomes secreted by human umbilical cord-derived mesenchymal stem cells promoted cartilage regeneration in OA rats. The levels of synovial fluid cytokines (TNF-alpha, IL-1 beta, and IL-6) were significantly reduced in the synovial fluid of exosome treated group, and exosome treatment also significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1 beta.
引用
收藏
页码:803 / 811
页数:9
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