ArticleStem cells translational medicine2026
The mitochondria-targeting compound PTC299 enhances megakaryocyte and platelet production.
Article in Stem cells translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroudThrombocytopenia is a common complication of various clinical conditions, resulting from impaired megakaryocyte function, reduced platelet production, or excessive platelet destruction. Current treatments, including platelet transfusions and thrombopoietin receptor agonists, are limited by platelet supply constraints and risks such as thrombotic complications. Emerging research highlights the role of mitochondrial-related biological processes or components in thrombopoiesis, yet targeted therapeutics remain scarce.
methodsIn this study, we investigated mitochondria-targeted compounds for their potential to enhance megakaryocyte and platelet productionusing a fetal liver megakaryocyte differentiation and platelet culture system, and explored their effects on in vivo megakaryocyte and platelet production using a radiation damage-induced thrombocytopenia mouse model.
resultsOur findings identify PTC299, a dihydroorotate dehydrogenase and VEGFA mRNA translation inhibitor, as a promising pro-plateletogenic agent. PTC299 not only enhances megakaryocyte and platelet production in vitro but also accelerates their recovery in a mouse model of radiation-induced thrombocytopenia. Additionally, PTC299 alleviates irradiation-induced splenomegaly.
conclusionPTC299 promotes megakaryocyte differentiation and platelet generation both in vitro and in vivo, demonstrating potential values for thrombocytopenia treatment and platelet regeneration.
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