Ex vivo platelet production system

¹Center for iPS Cell Research and Application, Kyoto University, Kyoto, ²Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan

Platelet products are provided from blood banks which collect blood from healthy donors. However, approximately 5% of platelet transfusion patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against class I human leukocyte antigens (HLA-I) or human platelet antigens (HPA). But for patients with rare HLA-I or HPA, donors are difficult to find. Aiming to ultimately solve this issue, we had developed ex vivo production system of iPS cell-derived platelet products (iPSC-PLTs), which were based on our technologies, megakaryocyte cell lines (imMKCLs) from patient iPSCs (Cell Stem Cell, 2014; Blood Advances, 2022), turbulent flow bioreactor (Cell, 2018) and new drugs (Blood Advances, 2017; Stem Cells Trans Med, 2017). The iPLAT1 study was conducted from 2019 to 2020 as the first-in-human clinical trial of iPSC-PLTs (Blood, 2022). The subject was a patient with aplastic anaemia complicated by anti-HPA-1a antibody-induced allo-PTR and had no matched HPA-1b/1b donor in Japan. Three dose cohort studies, as a dose-escalation fashion, allowed us to consider possible problems with the post-transfusion measurement method and the circulation capacity of the iPSC-PLTs. I would like to discuss scientific points towards further improvement of ex vivo manufacturing of iPSC-PLTs in my talk.