Tianjin Medical University Eye Center, Tianjin Medical University Eye Institute, China.
Exp Eye Res. 2012 Sep;102:44-9. doi: 10.1016/j.exer.2012.06.008. Epub 2012 Jul 16.
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 evaluated, 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.
间充质干细胞（MSCs）是一种有前途的免疫调节治疗候选物，目前正在几种器官移植排斥模型中进行测试。在这项研究中，我们在大鼠角膜同种异体移植排斥模型中测试了 MSC 注射的免疫调节作用。MSCs 从 Wistar 大鼠的骨髓中分离和培养。使用 Wistar 大鼠作为供体和 Lewis 大鼠作为受体建立大鼠角膜同种异体移植排斥模型。Lewis 大鼠随机分为 12 组，分别用单独的 MSCs 或不同剂量的 MSCs 联合环孢素 A（CsA）治疗。在 MSC 治疗的大鼠中，评估了 T 细胞对 ConA 的反应，测量了 T 淋巴细胞产生的 Th1/Th2 细胞因子，并评估了 CD4+CD25+Foxp3+调节性 T 细胞（Treg）的数量。结果表明，术后注射 MSCs 可延长移植物存活时间。MSCs 显著抑制体外致病性 T 细胞的增殖，并防止体内 T 细胞反应（p<0.05）。术后注射还降低了来自角膜移植大鼠的 T 淋巴细胞产生的 Th1 促炎细胞因子，并增加了 IL-4 细胞因子的分泌。此外，MSC 治疗可上调 Treg。出乎意料的是，与单独术后 MSC 治疗相比，应用 MSCs 联合低剂量 CsA 治疗（1mg/kg）加速了移植物排斥。然而，当 2mg/kg CsA 与 MSCs 一起给予时，移植物存活时间显著延长。这些结果表明 MSCs 可以对抗角膜同种异体移植排斥发挥治疗作用，并且需要进一步研究 MSCs 与 CsA 的联合治疗，因为观察到 CsA 剂量依赖性的相反作用。
