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Feeder-Free Derivation of Functional Platelets from Human Induced Pluripotent Stem Cells

Pei-Ju Sung, Sayandip Mukherjee, Michael P Blundell and Adrian J Thrasher

Derivation of patient specific induced pluripotent stem cells, in combination with directed platelet differentiation, provides a promising platform to study human thrombopoiesis or platelet disorders, and has clear potential for future clinical applications. However, efficient differentiation of human induced pluripotent stem cells (iPSCs) into functional blood cells remains challenging. In this study, we report a novel protocol for the generation of CD41a+, CD42b+, and CD61+ functional platelets from human iPSCs under feeder-free culture conditions. Platelets derived from this feeder-free system showed similar fibrinogen binding activity after agonist stimulation when compared to platelets derived from a previously reported cell line co culture system. Evidence showed these culture-derived platelets responded to different agonist stimulation by increased expression of activation markers (CD62P and PAC1) as expected. Together, these results provide an important step towards generating in vitro functional platelets from an unlimited source of patient-specific induced pluripotent stem cells using an animal component-free culture system.