Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells.
Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells.
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DOI：
10.1007/s00281-011-0266-8
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发表时间：
2011-11
影响因子：
9
通讯作者：
Dressel, Ralf
中科院分区：
文献类型：
--
作者：
Dressel, Ralf
关键词：
多能干细胞为再生医学带来了巨大的希望。它们可能会成为一系列新的细胞替代疗法的通用来源。干细胞来源的移植物临床应用的主要问题之一是免疫排斥和肿瘤形成的风险。多能性和致瘤性是多能干细胞密切相关的特征。然而，干细胞系或干细胞来源的移植物的遗传特征并不能充分描述形成畸胎瘤或其他肿瘤的能力。肿瘤的致瘤性总是取决于受体对致瘤细胞的排斥能力。本文综述了多能干细胞在免疫缺陷宿主、同基因宿主、异基因宿主和异种宿主中致瘤性的最新数据。对免疫抑制治疗和细胞分化的影响进行了讨论。不同的免疫效应机制似乎参与了未分化和分化的细胞群体的排斥反应。天然免疫系统的组成部分，如自然杀伤细胞和补体系统，在同基因受者中也是活跃的，似乎优先排斥未分化的细胞。这种作用可以降低免疫功能受者的肿瘤形成风险。在同种异体宿主中，细胞分化明显增加了适应性免疫系统对排斥反应的敏感性。目前的数据表明，受者的免疫系统对多能干细胞移植的结果有重大影响，无论是排斥反应、植入还是肿瘤发展。在解释实验性移植模型的结果时，必须考虑这一点，当计划将其转化为临床时，更要考虑这一点。
Pluripotent stem cells hold great promises for regenerative medicine. They might become useful as a universal source for a battery of new cell replacement therapies. Among the major concerns for the clinical application of stem cell-derived grafts are the risks of immune rejection and tumor formation. Pluripotency and tumorigenicity are closely linked features of pluripotent stem cells. However, the capacity to form teratomas or other tumors is not sufficiently described by inherited features of a stem cell line or a stem cell-derived graft. The tumorigenicity always depends on the inability of the recipient to reject the tumorigenic cells. This review summarizes recent data on the tumorigenicity of pluripotent stem cells in immunodeficient, syngeneic, allogeneic, and xenogeneic hosts. The effects of immunosuppressive treatment and cell differentiation are discussed. Different immune effector mechanisms appear to be involved in the rejection of undifferentiated and differentiated cell populations. Elements of the innate immune system, such as natural killer cells and the complement system, which are active also in syngeneic recipients, appear to preferentially reject undifferentiated cells. This effect could reduce the risk of tumor formation in immunocompetent recipients. Cell differentiation apparently increases susceptibility to rejection by the adaptive immune system in allogeneic hosts. The current data suggest that the immune system of the recipient has a major impact on the outcome of pluripotent stem cell transplantation, whether it is rejection, engraftment, or tumor development. This has to be considered when the results of experimental transplantation models are interpreted and even more when translation into clinics is planned.
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