Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Int J Mol Med. 2013 Dec;32(6):1337-44. doi: 10.3892/ijmm.2013.1529. Epub 2013 Oct 16.
Accumulating evidence has established the use of mesenchymal stem cells (MSCs) as candidate cells for immunosuppressive therapy. Experimental studies have suggested that MSCs exert their immunomodulatory effects through the induction of regulatory T cells (Tregs) in vitro and in vivo. However, the interactions between MSCs and Tregs in inflammatory bowel disease (IBD) and whether MSCs can be used for the treatment of IBD remains to be elucidated. In this study, we aimed to investigate whether MSCs can be used for the treatment of IBD through the induction of Tregs. MSCs were isolated and identified by flow cytometry. The MSCs were transduced with a replication-defective recombinant lentiviral vector carrying GFP in order to be able to trace the injected cells in vivo. Prepared MSCs (1x106) were injected into rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)‑induced colitis via the tail vein; the control rats received phosphate-buffered saline (PBS) alone. Two weeks after the intravenous infusion, the frequency of CD4+CD25+Foxp3 cells in the peripheral blood was examined by flow cytometry. The colon was sectioned and analyzed for histopathological changes. Foxp3 mRNA expression was determined by real-time reverse-transcription polymerase chain reaction (qRT-PCR). In our study, the systemic infusion of MSCs significantly ameliorated the clinical and histopathologic severity of TNBS-induced colitis in contrast to the controls. There was an inverse regulation of mucosal and peripheral Foxp3 expression, suggesting that the MSCs redistributed the Tregs from the mucosa to the blood. Thus, MSCs exhibit immunomodulatory functions and may be used to ameliorate or treat IBD by redistributing regulatory T cells. Therefore, the interactions between transplanted bone marrow-derived MSCs and Tregs should be further investigated; MSCs have tremendous potential for use in the treatment of IBD.
越来越多的证据表明间充质干细胞（MSCs）可作为免疫抑制治疗的候选细胞。实验研究表明，MSCs 通过体外和体内诱导调节性 T 细胞（Tregs）发挥其免疫调节作用。然而，MSCs 与炎症性肠病（IBD）中的 Tregs 之间的相互作用以及 MSCs 是否可用于治疗 IBD 仍有待阐明。在这项研究中，我们旨在研究通过诱导 Tregs 是否可以使用 MSCs 来治疗 IBD。通过流式细胞术分离和鉴定 MSCs。将复制缺陷型重组慢病毒载体携带 GFP 转导 MSC，以便能够在体内追踪注射的细胞。通过尾静脉将准备好的 MSC（1x106）注入 2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎大鼠中；对照组大鼠仅接受磷酸盐缓冲盐水（PBS）。静脉内输注两周后，通过流式细胞术检查外周血中 CD4+CD25+Foxp3 细胞的频率。对结肠进行切片并分析组织病理学变化。通过实时逆转录聚合酶链反应（qRT-PCR）确定 Foxp3 mRNA 表达。在我们的研究中，与对照组相比，MSC 的系统输注可显著改善 TNBS 诱导的结肠炎的临床和组织病理学严重程度。粘膜和外周 Foxp3 表达呈反向调节，表明 MSC 将 Tregs 从粘膜重新分布到血液中。因此，MSC 表现出免疫调节功能，通过重新分布调节性 T 细胞，可用于改善或治疗 IBD。因此，应该进一步研究移植骨髓来源的 MSC 和 Tregs 之间的相互作用；MSC 在治疗 IBD 方面具有巨大的潜力。
