First evidence of the circulation of induced pluripotent stem cell-derived platelets in humans

Abstract

Abstract Platelet products are essential for preventing and treating bleeding in patients with thrombocytopenia. However, their short shelf life and reliance on voluntary blood donations pose significant challenges to maintaining a stable supply. To overcome these limitations, induced pluripotent stem cell-derived platelets (iPSC-PLTs) have emerged as a promising alternative. The clinical application of iPSC-PLTs succeeded in demonstrating safety in an autologous transfusion setting; however, allogeneic applications remain unexplored. Here, we report the world’s first clinical evaluation of an allogeneic iPSC-PLT product. An immortalized megakaryocyte cell line (imMKCL) was established from an iPSC line by introducing 3 inducible genes—c-MYC, BMI1, and BCL-XL—and subsequently generating master and working cell banks. Using the working cell bank and turbulent flow bioreactors, an allogeneic iPSC-PLT product, MEG-002, was successfully produced with clinically relevant quality and yield. MEG-002 underwent comprehensive structural and functional characterization, including in vivo efficacy testing in rabbit models, which confirmed its functionality. Preclinical safety studies revealed no concerns. A clinical trial was conducted in accordance with ethical and regulatory standards in Japan. MEG-002 was infused into a patient with aplastic anemia at a dose of 6 × 1010 platelets. No adverse events were reported, and no clinically significant changes were observed in any assessments. Furthermore, a transient increase in platelet count and evidence of iPSC-PLT circulation were observed. Despite being descriptive observations from a single subject, these findings suggest the safety and potential efficacy of allogeneic iPSC-PLTs in humans. The clinical trial is registered with the Japan Registry of Clinical Trials (jRCT2053210068).