Immunomodulatory effects of stem cells
Immunomodulatory effects of stem cells
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DOI：
10.1111/prd.12024
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发表时间：
2013-10-01
影响因子：
18.6
通讯作者：
Bartold, P. Mark
中科院分区：
文献类型：
--
作者：
Wada, Naohisa;Gronthos, Stan;Bartold, P. Mark
在过去的二十年中，成人间充质干细胞因其在组织工程中的潜在用途而受到相当大的关注，主要是因为它们具有分化成多种基质细胞谱系的潜力。最近，间充质干细胞的免疫调节特性作为这些细胞的独特特性引起了人们的兴趣，这些细胞可以用于免疫介导疾病的新治疗方法。间充质干细胞在体外和体内均显示出抑制活化的T细胞的增殖，但刺激调节性T细胞增殖。还已知间充质干细胞具有弱免疫原性，并通过各种机制对B细胞、自然杀伤细胞、树突细胞和嗜中性粒细胞发挥免疫抑制作用。此外，同种异体间充质干细胞的静脉内给药已经显示出在大器官移植排斥的临床前动物模型和各种基于自身免疫和炎症的疾病中对宿主免疫反应的显著抑制。一些利用人间充质干细胞的临床试验也在移植物与非移植物的患者中产生了有希望的结果。宿主疾病和自身免疫性疾病。从各种牙齿组织中鉴定的间充质干细胞，包括牙周膜干细胞，也具有多能性和免疫调节特性。因此，牙齿间充质干细胞可能代表一种替代细胞来源，不仅用于组织再生，而且还可用于治疗自身免疫性和炎症介导的疾病。这些发现引起了人们对牙组织间充质干细胞作为替代细胞来源的兴趣，用于在移植到人类白细胞抗原不匹配的供体后的组织再生过程中调节同种异体反应性。为了研究牙周再生的潜力，未来的工作将需要评估同种异体牙周膜干细胞在牙周病动物模型中再生牙周膜的能力。本综述介绍了间充质干细胞对各种类型的免疫细胞的免疫抑制作用，通过它们发挥其作用模式的潜在机制，以及利用间充质干细胞的临床前动物研究和人体临床试验，包括来自牙齿结构的人群。
Adult-derived mesenchymal stem cells have received considerable attention over the past two decades for their potential use in tissue engineering, principally because of their potential to differentiate into multiple stromal-cell lineages. Recently, the immunomodulatory properties of mesenchymal stem cells have attracted interest as a unique property of these cells that may be harnessed for novel therapeutic approaches in immune-mediated diseases. Mesenchymal stem cells have been shown to inhibit the proliferation of activated T-cells both in vitro and in vivo but to stimulate T-regulatory cell proliferation. Mesenchymal stem cells are also known to be weakly immunogenic and to exert immunosuppressive effects on B-cells, natural killer cells, dendritic cells and neutrophils through various mechanisms. Furthermore, intravenous administration of allogeneic mesenchymal stem cells has shown a marked suppression of host immune reactions in preclinical animal models of large-organ transplant rejection and in various autoimmune- and inflammatory-based diseases. Some clinical trials utilizing human mesenchymal stem cells have also produced promising outcomes in patients with graft-vs.-host disease and autoimmune diseases. Mesenchymal stem cells identified from various dental tissues, including periodontal ligament stem cells, also possess multipotent and immunomodulatory properties. Hence, dental mesenchymal stem cells may represent an alternate cell source, not only for tissue regeneration but also as therapies for autoimmune- and inflammatory-mediated diseases. These findings have elicited interest in dental tissue mesenchymal stem cells as alternative cell sources for modulating alloreactivity during tissue regeneration following transplantation into human leukocyte antigen-mismatched donors. To examine this potential in periodontal regeneration, future work will need to assess the capacity of allogeneic periodontal ligament stem cells to regenerate periodontal ligament in animal models of periodontal disease. The present review describes the immunosuppressive effects of mesenchymal stem cells on various types of immune cells, the potential mechanisms through which they exert their mode of action and the preclinical animal studies and human clinical trials that have utilized mesenchymal stem cells, including those populations originating from dental structures.