Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Semin Immunopathol. 2011 Nov;33(6):563-72. doi: 10.1007/s00281-011-0269-5. Epub 2011 Apr 11.
The potential to develop into any tissue makes pluripotent stem cells (PSCs) one of the most promising sources for cellular therapeutics. However, numerous hurdles exist to their clinical applications, three of the most concerning include the inability to separate therapeutic population from heterogeneously differentiated cultures, the risk of teratoma formation from residual pluripotent cells, and immunologic rejection of engrafted cells. The recent development of induced PSCs has been proposed as a solution to the histocompatibility barrier. Theoretically, creation of patient-specific induced PSC lines would exhibit a complete histocompatibility antigen match. However, regardless of the PSC source, in vitro propagation and nonphysiologic differentiation may result in other, likely less powerful, mechanisms of immune rejection. In light of recent progress towards clinical application, this review focuses on two such potential immunologic mechanisms applicable to isogenic PSC derivates: namely, the immunogenicity of aberrant antigens resulting from long-term in vitro maintenance and alterations in immunologic properties due to rapid in vitro differentiation. These issues will be considered with attention to their relation to effector cells in the adult immune system. In addition, we highlight immunosuppressive approaches that could potentially address the immunogenicity of these proposed mechanisms.
多能干细胞（PSCs）具有分化为任何组织的潜能，是细胞治疗中最有前途的来源之一。然而，其临床应用存在诸多障碍，其中最令人担忧的有三个，包括无法从异质分化培养物中分离出治疗群体、残留多能细胞形成畸胎瘤的风险，以及植入细胞的免疫排斥。最近诱导多能干细胞的发展被提出作为解决组织相容性障碍的一种方法。从理论上讲，创建患者特异性诱导多能干细胞系将表现出完全的组织相容性抗原匹配。然而，无论 PSC 的来源如何，体外繁殖和非生理分化可能导致其他、可能不太强大的免疫排斥机制。鉴于最近在临床应用方面取得的进展，本综述重点关注两种适用于同基因 PSC 衍生物的潜在免疫机制：即，长期体外维持导致的异常抗原的免疫原性和由于快速体外分化导致的免疫特性改变。这些问题将被考虑到与成人免疫系统中的效应细胞的关系。此外，我们强调了潜在的免疫抑制方法，这些方法可能解决这些拟议机制的免疫原性。
