Sackett S D, Brown M E, Tremmel D M, Ellis T, Burlingham W J, Odorico J S
Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
Transplant Rev (Orlando). 2016 Apr;30(2):61-70. doi: 10.1016/j.trre.2016.02.001. Epub 2016 Feb 10.
Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs. autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives.
诱导多能干细胞（iPSC）衍生的组织是构建各种再生医学疗法的一种很有前景的细胞来源；从简单的细胞移植到在脱细胞器官中重新接种细胞以重建多细胞组织。尽管用于产生iPSC的重编程策略已经有所改进，但iPSC的临床应用受到独特的人类白细胞抗原（HLA）基因的限制，这是移植的主要免疫障碍。为了克服与同种异体组织和器官相关的免疫障碍，生成与患者组织相容的iPSC（自体或HLA匹配的细胞）为个性化医学提供了一个有吸引力的平台。然而，由于不同细胞系的分化潜能不同，以及在重编程过程中可能出现的遗传和表观遗传异常的识别，人们对iPSC衍生物的健康适应性、安全性和免疫原性提出了担忧。此外，高昂的成本和监管障碍可能在短期内阻碍患者特异性疗法的商业化。尽管如此，最近的研究提供了一些使用自体iPSC具有免疫益处的证据。然而，还需要更多的研究来评估各种自体和同种异体人iPSC衍生细胞类型的免疫原性，并测试各种消除排斥反应的方法。在这里，我们阐述了使用同种异体和自体iPSC进行移植治疗的观点，以及各自在分化潜能、免疫原性、遗传稳定性和致瘤性方面的优缺点。我们还回顾了关于同基因iPSC免疫原性的当前文献，并讨论了质疑HLA匹配的iPSC库可行性的证据。最后，我们将讨论消除或减少宿主对PSC衍生物免疫反应的新兴方法。
