Stepwise model for platelet manufacturing. (A) Self-replicating human PSCs can be genetically manipulated using genome-editing technologies.⁶⁷  (B) Current PSC-differentiation systems generate primitive MEPs and megakaryocytes,^20,21  but recent protocol advancements⁷⁹  may enable future systems to generate definitive-like MEPs and megakaryocytes. Self-replicating MEPs have been generated using PSCs with inducible systems to regulate the expression level of transgenes or endogenous transcription factors.^41,57  (C-D) Megakaryocyte maturation and PPF may be induced using different matrices, modulators of apoptosis, and shear stress.^65,66  Platelet release could also be induced from mature megakaryocytes by inflammatory induced rupture of the cell.⁶³  Professional illustration by Somersault18:24.