Jiamvoraphong N.Lorthongpanich C.Septham P.Klaihmon P.Kheolamai P.Laowtammathron C.Imsoonthornruksa S.Ketudat-Cairns M.Issaragrisil S.Mahidol University2026-06-212026-06-212026-06-01Cell Biology International Vol.50 No.6 (2026)10656995https://repository.li.mahidol.ac.th/handle/123456789/117453Platelet shortages and limited storage stability restrict global platelet transfusion capacity, highlighting the need for efficient in vitro platelet production systems. This study establishes a simple, non-genetic and cost-effective system for efficient in vitro platelet-like particle (PLP) production from human hematopoietic stem/progenitor cells (HSPCs) using a Phase-specific modulation of Hippo-YAP/TAZ signaling modulation. Temporal control of Hippo-YAP/TAZ signaling by lysophosphatidic acid (LPA), an activator of YAP/TAZ activity, significantly enhanced megakaryocyte differentiation, expansion and PLP production, resulting in an approximately 15-fold increase in PLP yield at the end of the procedure. Furthermore, LPA extended the expansion period of HSPC-derived megakaryocytes up to 8 days, resulting in a greater than 20-fold increase in the number of HSPC-derived CD41⁺ megakaryocytes. Moreover, replacement of expensive commercial recombinant human thrombopoietin (C-rhTPO), one of the major cost-driving components in in vitro PLP production, with recombinant human thrombopoietin produced in Escherichia coli (W-rhTPO) further improved the cost-effectiveness of the procedure. In conclusion, this study demonstrates that temporally controlled Hippo-YAP/TAZ signaling, together with affordable cytokine supplementation, provides a robust and GMP-compatible platform for large-scale PLP manufacturing for future clinical applications. We believe that this system will enable scalable PLP generation, even in resource-constrained settings, to increase human platelet supply for many life-saving therapies in the future.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1002/cbin.701772-s2.0-10504177421110958355