Sugimoto Naoshi, Eto Koji
Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University.
Department of Regenerative Medicine, Chiba University Graduate School of Medicine.
Rinsho Ketsueki. 2022;63(10):1430-1439. doi: 10.11406/rinketsu.63.1430.
The COVID-19 pandemic has cast a shadow over transfusion medicine based on the blood donation system. However, managing alloimmune platelet transfusion refractoriness (allo-PTR) has already been difficult. As a first step toward resolving this issue using induced pluripotent stem cell-derived platelet products (iPSC-PLTs), a clinical trial of autologous products (iPLAT1) was conducted in a patient with allo-PTR caused by anti-HPA-1a antibodies who had no compatible donor, and safety was confirmed. To produce iPSC-PLTs, a master cell bank (MCB) of expandable megakaryocyte lines (imMKCLs) is established from iPSCs. From this MCB, iPSC-PLTs are manufactured using a newly developed turbulent-type bioreactor and various compounds. Their quality, safety, and efficacy are confirmed by extensive preclinical studies. Based on the findings of the iPLAT1 study, a clinical trial of allo-transfusion of HLA homozygous iPSC-PLTs is currently ongoing and HLA class I-deficient O-type universal iPSC-PLTs are also being developed. iPSC-PLTs are expected to solve various problems, including allo-PTR in platelet transfusion, and greatly contribute to the advancement of transfusion medicine.
新型冠状病毒肺炎疫情给基于献血系统的输血医学蒙上了一层阴影。然而,管理同种免疫性血小板输注无效(allo-PTR)一直都很困难。作为使用诱导多能干细胞衍生血小板产品(iPSC-PLTs)解决这一问题的第一步,对一名因抗HPA-1a抗体导致allo-PTR且无相合供者的患者进行了自体产品的临床试验(iPLAT1),并确认了安全性。为了生产iPSC-PLTs,从诱导多能干细胞建立了可扩增巨核细胞系(imMKCLs)的主细胞库(MCB)。从这个MCB中,使用新开发的湍流型生物反应器和各种化合物制造iPSC-PLTs。通过广泛的临床前研究确认了它们的质量、安全性和有效性。基于iPLAT1研究的结果,目前正在进行HLA纯合iPSC-PLTs同种输血的临床试验,并且也正在开发HLA I类缺陷O型通用iPSC-PLTs。iPSC-PLTs有望解决包括血小板输注中的allo-PTR在内的各种问题,并为输血医学的发展做出巨大贡献。