Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Ann Hematol. 2013 Oct;92(10):1295-308. doi: 10.1007/s00277-013-1796-z. Epub 2013 May 31.
Mesenchymal stem cells (MSCs) have emerged as a therapeutic approach in a range of medical fields, including regenerative medicine, cancer, autoimmune diseases, and inflammatory diseases, because of their unique properties of tissue repair and major histocompatibility complex-unmatched immunosuppression. Because both in vitro and in vivo findings demonstrate that MSCs possess potent immunoregulatory functions, there has been increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation, especially in the prevention and treatment of graft-versus-host disease (GVHD). GVHD is a major cause of transplantation-related mortality, and conventional immunosuppressants frequently fail to treat patients suffering from GVHD. Following Ringden's pilot study that used third-party MSCs to treat a steroid-refractory GVHD patient, MSCs have created growing interest as a therapeutic agent for GVHD. There have been further studies which demonstrated the potentials of MSC treatment in steroid-refractory GVHD, de novo GVHD, and also GVHD prevention. However, MSCs still present limitations. The need for MSCs to be "licensed" in a pro-inflammatory environment, especially in the presence of interferon gamma, allows only a narrow window for their administration. Thus, their effects have been less clear as a preventive measure before the inflammatory environment of GVHD is established and also when administered during a chronic setting where MSCs may be alternatively licensed. In this review, we focus on the immunomodulatory properties of MSCs and their effects in relation to GVHD. Given the efficacy of MSCs in murine models of GVHD and their safety in clinical trials, it is crucial that larger clinical trials are conducted and further modifications are investigated.
间充质干细胞 (MSCs) 因其组织修复和主要组织相容性复合体不匹配的免疫抑制等独特特性，已成为再生医学、癌症、自身免疫性疾病和炎症性疾病等多个医学领域的治疗方法。由于体外和体内研究结果均表明 MSCs 具有强大的免疫调节功能，因此人们对 MSCs 在异基因造血干细胞移植中的作用越来越感兴趣，特别是在预防和治疗移植物抗宿主病 (GVHD) 方面。GVHD 是移植相关死亡的主要原因，常规免疫抑制剂常常无法治疗 GVHD 患者。在 Ringden 进行了使用第三方 MSCs 治疗类固醇难治性 GVHD 患者的试点研究后，MSC 作为 GVHD 治疗药物引起了越来越多的关注。进一步的研究表明，MSC 治疗在类固醇难治性 GVHD、新发 GVHD 以及 GVHD 预防方面具有潜力。然而，MSC 仍然存在一些局限性。在促炎环境中，特别是在干扰素 γ 存在的情况下，需要对 MSCs 进行“许可”，这仅为其给药提供了一个狭窄的窗口。因此，在 GVHD 的炎症环境建立之前作为预防措施，以及在 MSCs 可能被替代许可的慢性环境中给药时，其效果不太明确。在这篇综述中，我们重点关注 MSCs 的免疫调节特性及其与 GVHD 的关系。鉴于 MSCs 在 GVHD 小鼠模型中的疗效及其在临床试验中的安全性，开展更大规模的临床试验并进一步研究改进方法至关重要。
