大鼠角膜同种异体移植排斥模型中间充质干细胞的免疫调节作用
建立大鼠角膜同种异体移植排斥模型，术后单用MSC或MSC 与环孢霉素A联合用药，检测相关指标，发现MSC能够通过抑制病理性T淋巴细胞增殖和抑制促炎症细胞因子的分泌，延长器官移植存活时间。但是低剂量的环孢霉素与MSC联合使用造成加速的移植排斥。提示MSC对大鼠角膜同种异体移植排斥具有治疗作用，其与环孢霉素的联合用药需要进一步研究。
6. Exp Eye Res. 2012 Sep;102:44-9. doi: 10.1016/j.exer.2012.06.008. Epub 2012 Jul 16.
Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model.
Jia Z, Jiao C, Zhao S, Li X, Ren X, Zhang L, Han ZC, Zhang X.
Source
Tianjin Medical University Eye Center, Tianjin Medical University Eye Institute, China.
Abstract
Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in several organ transplant rejection models. In this study, we tested the immunomodulatory effects of MSC injection in a rat model of corneal allograft rejection. MSCs were isolated and cultured from bone marrow of Wistar rats. A rat corneal allograft rejection model was established using Wistar rats as donors and Lewis rats as recipients. Lewis rats were randomly separated into 12 groups and treated with MSCs alone or MSCs combined with Cyclosporin A (CsA) at different doses. In MSC-treated rats, the T cell response to ConA was evalsuated, Th1/Th2 cytokines produced by T lymphocytes were measured, and the number of CD4+CD25+Foxp3+ regulatory T cells (Treg) was assessed. Results demonstrated that postoperative injection of MSCs prolonged graft survival time. MSCs significantly inhibited proliferation of pathogenic T cells in vitro and prevented T cell response in vivo (p < 0.05). Postoperative injection also reduced Th1 pro-inflammatory cytokines and elevated IL-4 cytokine secretion from T lymphocytes derived from cornea-transplanted rats. In addition, Tregs were upregulated by MSC treatment. Unexpectedly, the application of MSCs combined with low dose CsA therapy (1 mg/kg) accelerated graft rejection compared with postoperative MSC therapy alone. However, when 2 mg/kg CsA was given together with MSCs, graft survival was significantly prolonged. These results suggested that MSCs could exert therapeutic effect against corneal allograft rejection, and further investigation of combined MSC and CsA treatment be required as opposite effects were observed depending on CsA dose.
