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在治疗小鼠胶原诱导性关节炎方面,CD146+间充质干细胞比CD146-细胞显示出更大的治疗潜力。

CD146+ mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice.

作者信息

Wu Cheng-Chi, Liu Fei-Lan, Sytwu Huey-Kang, Tsai Chang-Youh, Chang Deh-Ming

机构信息

Graduate Institute of Life Sciences, National Defense Medical Center, No.161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei, 114, Taiwan, Republic of China.

Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District., Taipei, 112, Taiwan, Republic of China.

出版信息

Stem Cell Res Ther. 2016 Feb 3;7:23. doi: 10.1186/s13287-016-0285-4.

Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

间充质干细胞(MSC)亚型的特征和治疗潜力在很大程度上尚不清楚。在本研究中,从人脐带中分离出CD146(+)和CD146(-)间充质干细胞,并研究了它们对调节性T细胞(Treg)、Th17细胞、软骨生成和成骨的影响。

方法

采用流式细胞术定量CD146(+)和CD146(-)间充质干细胞上表达的IL-6和TGF-β1。通过将细胞关节内(IA)转移到胶原诱导性关节炎(CIA)小鼠体内后测量临床评分和关节组织学来确定这两个亚群的治疗潜力。

结果

与CD146(-)间充质干细胞相比,CD146(+)间充质干细胞表达的IL-6较少,对软骨生成的影响显著更大。T淋巴细胞激活后,在体外和体内,Th17细胞在暴露于CD146(-)细胞时被激活,但暴露于CD146(+)细胞时未被激活。IA注射CD146(+)间充质干细胞可减轻CIA的进展。免疫组织化学显示,在CIA小鼠的软骨中仅检测到HLA-A(+) CD146(+)细胞。这些细胞可能有助于保留蛋白聚糖表达。

结论

本研究表明,CD146(+)细胞在软骨保护方面比CD146(-)细胞具有更强的效力,并且可以抑制Th17细胞的激活。这些数据表明CD146(+)细胞在治疗炎性关节炎方面具有潜在的治疗应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d4a/4741021/b53680608953/13287_2016_285_Fig1_HTML.jpg

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