Sullivan Stephen, Fairchild Paul J, Marsh Steven G E, Müller Carlheinz R, Turner Marc L, Song Jihwan, Turner David
Global Alliance for iPSC Therapies, Jack Copland Centre, Heriot-Watt Research Park, Edinburgh, UK.
University of Oxford, Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
Stem Cell Res. 2020 Dec;49:102035. doi: 10.1016/j.scr.2020.102035. Epub 2020 Oct 29.
The development of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka and colleagues in 2006 has led to a potential new paradigm in cellular therapeutics, including the possibility of producing patient-specific, disease-specific and immune matched allogeneic cell therapies. One can envisage two routes to immunologically compatible iPSC therapies: using genetic modification to generate a 'universal donor' with reduced expression of Human Leukocyte Antigens (HLA) and other immunological targets or developing a haplobank containing iPSC lines specifically selected to provide HLA matched products to large portions of the population. HLA matched lines can be stored in a designated physical or virtual global bank termed a 'haplobank'. The process of 'iPSC haplobanking' refers to the banking of iPSC cell lines, selected to be homozygous for different HLA haplotypes, from which therapeutic products can be derived and matched immunologically to patient populations. By matching iPSC and derived products to a patient's HLA class I and II molecules, one would hope to significantly reduce the risk of immune rejection and the use of immunosuppressive medication. Immunosuppressive drugs are used in several conditions (including autoimmune disease and in transplantation procedures) to reduce rejection of infused cells, or transplanted tissue and organs, due to major and minor histocompatibility differences between donor and recipient. Such regimens can lead to immune compromise and pathological consequences such as opportunistic infections or malignancies due to decreased cancer immune surveillance. In this article, we will discuss what is practically involved if one is developing and executing an iPSC haplobanking strategy.
2006年，山中伸弥及其同事诱导多能干细胞（iPSC）的研发，为细胞治疗带来了潜在的新范例，其中包括生产患者特异性、疾病特异性和免疫匹配的同种异体细胞疗法的可能性。可以设想两条通往免疫兼容iPSC疗法的途径：利用基因改造来生成人类白细胞抗原（HLA）和其他免疫靶点表达降低的“通用供体”，或者建立一个单倍型库，其中包含经过特别挑选的iPSC系，以便为大部分人群提供HLA匹配的产品。HLA匹配的细胞系可以储存在一个指定的实体或虚拟全球库中，即“单倍型库”。“iPSC单倍型库构建”过程是指对iPSC细胞系进行库藏，这些细胞系被选来针对不同的HLA单倍型为纯合子，从中可以衍生出治疗产品，并在免疫上与患者群体相匹配。通过使iPSC及其衍生产品与患者的HLA I类和II类分子相匹配，有望显著降低免疫排斥风险以及免疫抑制药物的使用。免疫抑制药物用于多种情况（包括自身免疫性疾病和移植手术），以减少由于供体和受体之间主要和次要组织相容性差异而导致的注入细胞、移植组织和器官的排斥反应。这样的治疗方案可能导致免疫功能受损以及诸如机会性感染或因癌症免疫监视降低而引发的恶性肿瘤等病理后果。在本文中，我们将讨论如果有人正在制定和实施iPSC单倍型库构建策略，实际会涉及哪些方面。
