[Lessons from the first-in-human clinical trial of iPSC-derived platelets: aiming to understand platelet biogenesis].

Abstract

The iPLAT1 study was conducted from 2019 to 2020 as the first-in-human clinical trial of iPS cell-derived platelet products (iPSC-PLTs). The subject was a patient with aplastic anemia refractory to anti-HPA-1a antibody-induced platelet transfusions who had no matched HPA-1b/1b donor. Autologous iPSC-PLTs were manufactured from a megakaryocyte cell line, imMKCL, established from the patient's iPSCs. High-efficiency manufacturing of iPSC-PLTs was achieved by incorporating the concept of turbulent flow in bioreactor tanks to mimic in vivo conditions. After comprehensive non-clinical studies, the iPLAT1 study was conducted as a dose-escalation study and achieved the primary endpoint of safety. However, an increase in the platelet count after transfusion was not observed, raising the possibility of a failure in post-transfusion measurement or defective circulation of transfused iPSC-PLTs. Since then, my research team and I have been conducting reverse-translational research to improve imMKCLs and developing a larger-scale manufacturing system to improve turbulent flow in bioreactor tanks. We have also recently demonstrated properties of subset of immune megakaryocytes in imMKCLs. Building upon such efforts, we have newly begun R&D for next-generation iPSC-PLTs.