Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis.
Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis.
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诱导多能干细胞源性间充质干细胞与滑膜源性间充质干细胞分泌的外泌体治疗骨关节炎的比较
DOI：
10.1186/s13287-017-0510-9
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发表时间：
2017-03-09
影响因子：
7.5
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhu Y;Wang Y;Zhao B;Niu X;Hu B;Li Q;Zhang J;Ding J;Chen Y;Wang Y
骨关节炎（Osteoarthritis，OA）是世界范围内最常见的关节疾病。在过去的十年中，间充质干细胞（MSCs）已被广泛用于治疗OA。基于MSC的疗法的潜在机制已归因于营养因子的旁分泌，其中外泌体可能起主要作用。在这项研究中，我们的目的是比较分泌的外泌体滑膜间充质干细胞（SMMSC-Exos）和外泌体诱导多能干细胞衍生的间充质干细胞（iMSC-Exos）对治疗OA的有效性。方法诱导多能干细胞衍生的间充质干细胞和滑膜间充质干细胞的特点，通过流式细胞术。使用超滤方法分离iMSC-Exos和SMMSC-Exos。可调电阻脉冲传感分析，透射电子显微镜，和蛋白质印迹被用来确定外来体。在胶原酶诱导的OA小鼠模型中关节内注射iMSC-Exos和SMMSC-Exos，并通过肉眼、组织学和免疫组织化学分析评估外泌体注射的功效。我们还评估了iMSC-Exos和SMMSC-Exos对人软骨细胞增殖和迁移的影响，通过细胞计数和划痕试验，分别ResultsThe大多数iMSC-Exos和SMMSC-Exos的直径约为50-150 nm，表达CD 9，CD 63和TSG 101。iMSC-Exos和SMMSC-Exos对小鼠OA模型均有明显的治疗作用，但iMSC-Exos的治疗效果优于SMMSC-Exos。同样，软骨细胞的迁移和增殖刺激iMSC-Exos和SMMSC-Exos，与iMSC-Exos发挥更强的effects.ConclusionsThe本研究表明，iMSC-Exos有更大的治疗效果比SMMSC-Exos对OA。由于自体iMSC在理论上是取之不尽的，iMSC-Exos可能代表了治疗OA的新治疗方法。
BackgroundOsteoarthritis (OA) is the most common joint disease worldwide. In the past decade, mesenchymal stem cells (MSCs) have been used widely for the treatment of OA. A potential mechanism of MSC-based therapies has been attributed to the paracrine secretion of trophic factors, in which exosomes may play a major role. In this study, we aimed to compare the effectiveness of exosomes secreted by synovial membrane MSCs (SMMSC-Exos) and exosomes secreted by induced pluripotent stem cell-derived MSCs (iMSC-Exos) on the treatment of OA.MethodsInduced pluripotent stem cell-derived MSCs and synovial membrane MSCs were characterized by flow cytometry. iMSC-Exos and SMMSC-Exos were isolated using an ultrafiltration method. Tunable resistive pulse-sensing analysis, transmission electron microscopy, and western blots were used to identify exosomes. iMSC-Exos and SMMSC-Exos were injected intra-articularly in a mouse model of collagenase-induced OA and the efficacy of exosome injections was assessed by macroscopic, histological, and immunohistochemistry analysis. We also evaluated the effects of iMSC-Exos and SMMSC-Exos on proliferation and migration of human chondrocytes by cell-counting and scratch assays, respectively.ResultsThe majority of iMSC-Exos and SMMSC-Exos were approximately 50–150 nm in diameter and expressed CD9, CD63, and TSG101. The injection of iMSC-Exos and SMMSC-Exos both attenuated OA in the mouse OA model, but iMSC-Exos had a superior therapeutic effect compared with SMMSC-Exos. Similarly, chondrocyte migration and proliferation were stimulated by both iMSC-Exos and SMMSC-Exos, with iMSC-Exos exerting a stronger effect.ConclusionsThe present study demonstrated that iMSC-Exos have a greater therapeutic effect on OA than SMMSC-Exos. Because autologous iMSCs are theoretically inexhaustible, iMSC-Exos may represent a novel therapeutic approach for the treatment of OA.