ArticleStem cell research & therapy2022
Ricolinostat promotes the generation of megakaryocyte progenitors from human hematopoietic stem and progenitor cells.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 19 citations in OpenAlex.
- Laboratory Assessment and Clinical Outlook forAnnals of laboratory medicine · 2026Review
- Efficient Generation of Megakaryocyte Progenitors and Platelets From HSPCs via JAK2/STAT3 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Research progress of megakaryocytes and platelets in lung injury.Annals of medicine · 2024Review
- Establishment of human hematopoietic organoids for evaluation of hematopoietic injury and regeneration effect.Stem cell research & therapy · 2024Article
- Interleukins in Platelet Biology: Unraveling the Complex Regulatory Network.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Baffled-flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function.Cell proliferation · 2023Article
- Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases.Frontiers in pharmacology · 2022Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEx vivo production of induced megakaryocytes (MKs) and platelets from stem cells is an alternative approach for supplying transfusible platelets. However, it is difficult to generate large numbers of MKs and platelets from hematopoietic stem cells and progenitor cells (HSPCs).
methodsTo optimize the differentiation efficiency of megakaryocytic cells from HSPCs, we first employed a platelet factor 4 (PF4)-promoter reporter and high-throughput screening strategy to screen for small molecules. We also investigated the effects and possible mechanisms of candidate small molecules on megakaryocytic differentiation of human HSPCs.
resultsThe small molecule Ricolinostat remarkably promoted the expression of PF4-promoter reporter in the megakaryocytic cell line. Notably, Ricolinostat significantly enhanced the cell fate commitment of MK progenitors (MkPs) from cord blood HSPCs and promoted the proliferation of MkPs based on cell surface marker detection, colony-forming unit-MK assay, and quantitative real-time PCR analyses. MkPs generated from Ricolinostat-induced HSPCs differentiated into mature MKs and platelets. Mechanistically, we found that Ricolinostat enhanced MkP fate mainly by inhibiting the secretion of IL-8 and decreasing the expression of the IL-8 receptor CXCR2.
conclusionThe addition of Ricolinostat to the culture medium promoted MkP differentiation from HSPCs and enhanced the proliferation of MkPs mainly by suppressing the IL-8/CXCR2 pathway. Our results can help the development of manufacturing protocols for the efficient generation of MKs and platelets from stem cells in vitro.
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