Scalable production of stem cell–derived artificial platelets: A safe alternative in the era of blood shortage

Abstract

Abstract Background Global platelet supply is facing increasing instability due to a declining donor population caused by aging societies and repeated pandemic outbreaks. This shortage severely impacts patients who require regular platelet transfusions and leaves them exposed to the residual risk of transfusion-transmitted infections inherent in donor-derived platelet products. Therefore, developing a safe, sustainable, and donor-independent source of functional platelets is an urgent unmet need. Methods We established an artificial platelet production platform based on human induced pluripotent stem cells (hiPSCs). hiPSCs were first differentiated into hematopoietic stem/progenitor cells, which were then sequentially induced into megakaryocyte progenitors and mature megakaryocytes under optimized culture conditions. Platelets were then mass-produced from the mature megakaryocytes using a scalable, bioreactor-based system. Results The generated artificial platelets expressed key surface markers, including CD41a and CD42b, and exhibited morphological characteristics comparable to native human platelets. Functional analyses confirmed aggregation capacity in vitro and hemostatic efficacy in an in vivo thrombocytopenia animal model. Process scale-up in liter-scale bioreactors demonstrated that large-scale production with high purity and reproducibility is feasible. We are currently optimizing upstream and downstream processes in bioreactors exceeding 50 L capacity to produce clinical-grade platelet products for future clinical trials. Conclusion Our stem cell–derived artificial platelet production platform shows strong potential as a safe and stable alternative to donor-derived platelet transfusions. This technology could address current supply challenges and reduce transfusion-transmitted infection risks. We expect that this approach will contribute significantly to securing a stable platelet supply and improving patient outcomes in transfusion and laboratory medicine.