CD146+ mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice.
CD146+ mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice.
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DOI：
10.1186/s13287-016-0285-4
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发表时间：
2016-02-03
影响因子：
7.5
通讯作者：
Chang DM
中科院分区：
文献类型：
--
作者：
Wu CC;Liu FL;Sytwu HK;Tsai CY;Chang DM
间充质干细胞（MSCs）亚型的特征和治疗潜力在很大程度上是未知的。在这项研究中，CD 146+和CD 146-MSC从人脐带中分离，并研究其对调节性T细胞（TCRs），Th 17细胞，软骨形成和成骨的影响。流式细胞术检测CD 146+和CD 146- MSCs表面IL-6和TGF-β1的表达。两个亚群的治疗潜力通过测量关节内（IA）转移细胞到患有胶原诱导的关节炎（CIA）的小鼠后的临床评分和关节组织学来确定。与CD 146- MSCs相比，CD 146 + MSCs表达更少的IL-6，并且对软骨形成具有显著更大的影响。T淋巴细胞活化后，Th 17细胞在体外和体内暴露于CD 146-细胞时被活化，而在暴露于CD 146+细胞时不被活化。IA注射CD 146 + MSC可减弱CIA的进展。免疫组化显示CIA小鼠软骨中仅检测到HLA-A+ CD 146+细胞。这些细胞可能有助于保持蛋白聚糖的表达。这项研究表明，CD 146+细胞比CD 146-细胞具有更大的软骨保护效力，并能抑制Th 17细胞活化。这些数据表明CD 146+细胞在治疗炎性关节炎中的潜在治疗应用。
The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. In this study, CD146+ and CD146– MSCs were separated from human umbilical cords, and their effects on regulatory T cells (Tregs), Th17 cells, chondrogenesis, and osteogenesis were investigated. Flow cytometry was used to quantify IL-6 and TGF-β1 expressed on CD146+ and CD146– MSCs. The therapeutic potential of both subpopulations was determined by measuring the clinical score and joint histology after intra-articular (IA) transfer of the cells into mice with collagen-induced arthritis (CIA). Compared with CD146– MSCs, CD146+ MSCs expressed less IL-6 and had a significantly greater effect on chondrogenesis. After T lymphocyte activation, Th17 cells were activated when exposed to CD146– cells but not when exposed to CD146+ cells both in vitro and in vivo. IA injection of CD146+ MSCs attenuated the progression of CIA. Immunohistochemistry showed that only HLA-A+ CD146+ cells were detected in the cartilage of CIA mice. These cells may help preserve proteoglycan expression. This study suggests that CD146+ cells have greater potency than CD146– cells for cartilage protection and can suppress Th17 cell activation. These data suggest a potential therapeutic application for CD146+ cells in treating inflammatory arthritis.