Liu Xin, Li Wenjuan, Fu Xuemei, Xu Yang
Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Division of Biological Sciences, University of California, San Diego, La Jolla, CA, United States.
Front Immunol. 2017 Jun 2;8:645. doi: 10.3389/fimmu.2017.00645. eCollection 2017.
Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient. The breakthrough of the technology to generate autologous-induced pluripotent stem cells (iPSCs) by nuclear reprogramming of patient's somatic cells raised the possibility that autologous iPSC-derived cells can be transplanted into the patients without the concern of immune rejection. However, accumulating data indicate that certain iPSC-derived cells can be immunogenic. In addition, the genomic instability associated with iPSCs raises additional safety concern to use iPSC-derived cells in human cell therapy. In this review, we will discuss the mechanism underlying the immunogenicity of the pluripotent stem cells and recent progress in developing immune tolerance strategies of human pluripotent stem cell (hPSC)-derived allografts. The successful development of safe and effective immune tolerance strategy will greatly facilitate the clinical development of hPSC-based cell therapy.
人类胚胎干细胞（hESCs）能够进行无限自我更新，并分化为人体中的所有细胞类型，因此在目前无法治愈的疾病（包括神经退行性疾病、心力衰竭和黄斑变性）的细胞治疗方面具有巨大潜力。正在进行的基于hESC的黄斑变性治疗临床试验所获得的有前景的安全性和有效性数据，进一步凸显了这种潜力。然而，基于hESC的治疗在临床应用中的一个主要挑战是受体对hESC来源细胞的同种异体免疫排斥。通过对患者体细胞进行核重编程来产生自体诱导多能干细胞（iPSCs）的技术突破，增加了将自体iPSC来源的细胞移植到患者体内而无需担心免疫排斥的可能性。然而，越来越多的数据表明某些iPSC来源的细胞可能具有免疫原性。此外，与iPSCs相关的基因组不稳定性给在人类细胞治疗中使用iPSC来源的细胞带来了更多安全问题。在这篇综述中，我们将讨论多能干细胞免疫原性的潜在机制以及人类多能干细胞（hPSC）来源的同种异体移植物免疫耐受策略开发的最新进展。安全有效的免疫耐受策略的成功开发将极大地促进基于hPSC的细胞治疗的临床发展。
