Key result
Small molecule inhibitors boost functional platelet release ~4-fold from megakaryocytes, showing robust in vivo function.
Why the study?
Drug screens that select megakaryocytes with enhanced ploidy, cell size, and granularity may identify drugs that enhance platelet yield and function from in vitro-grown megakaryocytes.
Do small molecule inhibitors enhance functional platelet release in vivo from in vitro-grown megakaryocytes?
Do small molecule inhibitors enhance functional platelet release in vivo from in vitro-grown megakaryocytes?
Small molecule inhibitors can enhance the yield and function of platelets from ex vivo-generated megakaryocytes, potentially improving platelet transfusion therapies.
May advance ex vivo platelet manufacturing; leaves open translation to human transfusion therapies.
cells; this was fourfold over nontreated megakaryocytes. The released platelets from drug-treated, but healthy, megakaryocytes contained similar percentages of young, uninjured platelets that robustly responded to agonists and were well incorporated into a growing thrombus in vivo as controls. These studies suggest that drug screens that select megakaryocytes with enhanced ploidy, cell size, and granularity may include a subset of drugs that can enhance the yield and function of platelets, and may have clinical application for ex vivo-generated megakaryocytes and platelet transfusion.
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Jarocha et al. (2018) studied this question. Small molecule inhibitors vs. Nontreated megakaryocytes was evaluated on Platelet release (fourfold increase). Small molecule inhibitors enhanced functional platelet release from in vitro-grown megakaryocytes fourfold compared to nontreated controls, with released platelets showing robust function in vivo.
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