Adoptive transfer of human gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis via suppression of Th1 and Th17 cells and enhancement of regulatory T cell differentiation.
Adoptive transfer of human gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis via suppression of Th1 and Th17 cells and enhancement of regulatory T cell differentiation.
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DOI：
10.1002/art.37894
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发表时间：
2013-05
影响因子：
--
通讯作者：
Zheng, Song Guo
中科院分区：
文献类型：
--
作者：
Chen, Maogen;Su, Wenru;Lin, Xiaohong;Guo, Zhiyong;Wang, Julie;Zhang, Qunzhou;Brand, David;Ryffel, Bernhard;Huang, Jiefu;Liu, Zhongmin;He, Xiaoshun;Le, Anh D.;Zheng, Song Guo
目前的方法不能治愈类风湿性关节炎（RA）。越来越多的证据表明，骨髓间充质干细胞（BMSCs）的操作可能具有治疗RA的潜力。虽然基于BMSC的治疗面临许多挑战，如有限的细胞可用性和降低的临床可行性，我们在此证明，牙龈来源的间充质干细胞（GMSC）的替代结果显着改善对已建立的胶原诱导性关节炎（CIA）的治疗效果。在DBA/1 J小鼠中用II型胶原（CII）和CFA免疫诱导CIA。在免疫后第14天将GMSC静脉内注射到小鼠中。在一些实验中，腹膜内注射PC61（抗-CD 25抗体）用于在关节炎小鼠中缺失Tcl 3。GMSCs可显著降低CIA DBA/1 J小鼠关节炎的严重程度和病理评分，并下调炎性细胞因子（IFN-γ、IL-17 A）的产生。GMSC的输注导致关节炎小鼠中CD 4 + CD 39 + Foxp 3+细胞的增加。这些增加在脾脏和LN中观察到，随后在滑液中观察到。Foxp 3 + Treg细胞频率增加，主要由Helios阴性细胞组成。当Treg细胞耗尽时，GMSC的输注部分干扰CIA的进展。用CD 39或CD 73抑制剂预处理GMSCs可显著逆转GMSCs对CIA的保护作用。GMSC在控制CIA病理中的作用主要取决于CD 39/CD 73信号，部分取决于CD 4 + CD 39 + Foxp 3 + Treg细胞的诱导。GMSCs为自身免疫性疾病的治疗提供了一种有前途的方法。
Current approaches offer no cures for rheumatoid arthritis (RA). Accumulating evidence has revealed that manipulation of bone-marrow mesenchymal stem cells (BMSCs) may have the potential to treat RA. While BMSC-based therapy faces many challenges such as limited cell availability and reduced clinical feasibility, we herein demonstrate that substitution of gingival-derived mesenchymal stem cells (GMSCs) results in significantly improved therapeutic effects on established collagen-induced arthritis (CIA). CIA has been induced with the immunization of type II collagen (CII) and CFA in DBA/1J mice. GMSCs were injected i.v. into mice on day 14 after immunization. In some experiments, injection of PC61 (anti-CD25 antibody) i.p. was used to delete Tregs in arthritic mice. Infusion of GMSCs in DBA/1J mice with CIA significantly decreased the severity of arthritis and pathology scores, and down-regulated inflammatory cytokine (IFN-γ, IL-17A) production. Infusion of GMSCs resulted in an increase in CD4+CD39+Foxp3+ cells in arthritic mice. These increases were noted early in spleen and LN and later in synovial fluid. The increased frequency of Foxp3+ Treg cells consisted of cells that were mainly Helios negative. Infusion of GMSCs partially interfered with the progress of CIA when Treg cells were depleted. Pre-treatment of GMSCs with CD39 or CD73 inhibitor significantly reversed the protective effect of GMSCs on CIA. The role of GMSCs in controlling CIA pathology mostly depends upon CD39/CD73 signals and partially upon the induction of CD4+CD39+Foxp3+ Treg cells. GMSCs provide a promising approach for the treatment of autoimmune diseases.
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影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
--
作者：
Gonzalez, Manuel A.;Gonzalez-Rey, Elena;Delgado, Mario
通讯作者：
Delgado, Mario
影响因子：
4.4
作者：
Patel, Shyam A.;Meyer, Justin R.;Rameshwar, Pranela
通讯作者：
Rameshwar, Pranela
影响因子：
4.4
作者：
Gottschalk, Rachel A.;Corse, Emily;Allison, James P.
通讯作者：
Allison, James P.
源自人类胚胎干细胞的成纤维细胞直接发育和修复 3D 人类皮肤等同物。
影响因子：
7.5
作者：
Shamis Y;Hewitt KJ;Carlson MW;Margvelashvilli M;Dong S;Kuo CK;Daheron L;Egles C;Garlick JA
通讯作者：
Garlick JA