Laboratory Assessment and Clinical Outlook for Ex Vivo-Produced Human Platelets and Megakaryocytes from Stem Cell Sources

초록

Platelet transfusions are essential for managing thrombocytopenia but have critical limitations, including a 5–7-day shelf-life causing wastage, alloimmune refractoriness in chronically transfused patients, and vulnerability to supply disruptions. Ex vivo platelet production from stem cells represents a transformative solution, evolving from initial hematopoietic stem cell approaches to induced pluripotent stem cell platforms with unlimited expansion and genetic tractability for universal platelet products. We critically reviewed the state and future trajectory of ex vivo platelet production, focusing on stem cell sources, manufacturing innovations, QC methods, and progression from laboratory concept to clinical reality. Key advances include immortalized megakaryocyte progenitor cell lines for scalable manufacturing; turbulence-based bioreactors that harness physiological shear stress to produce over 100 billion platelets/run; and comprehensive quality frameworks spanning cellular and molecular characterization, functional assays, and in vivo validation. We comparatively analyzed pioneering first-in-human clinical trials that collectively established the safety of iPSC-derived platelet transfusion and highlighted the translational challenges of achieving donor-comparable efficacy. We also highlighted the evolving corporate landscape, wherein companies pursue commercialization alongside national initiatives, including Korea’s 15-yr artificial blood program. Convergence between biological insight, engineering innovation, and sustained investment suggests that ex vivo platelet production can transform transfusion medicine. Remaining challenges include reducing costs and optimizing in vivo circulation of platelet products. Initial implementation will likely focus on high-value applications, such as transfusion for alloimmunized patients, before broader adoption. The long-term goal is to replace the vulnerable donor-dependent system with ondemand production of standardized, pathogen-free, and universally compatible platelets.

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