Back to Search
Start Over
Ricolinostat promotes the generation of megakaryocyte progenitors from human hematopoietic stem and progenitor cells
- Source :
- Stem Cell Research & Therapy, Vol 13, Iss 1, Pp 1-16 (2022), Stem Cell Research & Therapy
- Publication Year :
- 2021
-
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.
- Subjects :
- Medicine (General)
Research
Megakaryocyte progenitor
Medicine (miscellaneous)
Cell Differentiation
QD415-436
Cell Biology
Hematopoietic Stem Cells
Hydroxamic Acids
Biochemistry
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Ricolinostat
R5-920
Pyrimidines
Megakaryocyte
Molecular Medicine
Humans
Hematopoietic stem and progenitor cell
Megakaryocytes
Megakaryocyte Progenitor Cells
Subjects
Details
- ISSN :
- 17576512
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Stem cell researchtherapy
- Accession number :
- edsair.doi.dedup.....e16a1d3f43c56f388885b6754e707187