Flt3/Flk-2-ligand in synergy with thrombopoietin delays megakaryocyte development and increases the numbers of megakaryocyte progenitor cells in serum-free cultures initiated with CD34+ cells.

2.50
Hdl Handle:
http://hdl.handle.net/2336/30755
Title:
Flt3/Flk-2-ligand in synergy with thrombopoietin delays megakaryocyte development and increases the numbers of megakaryocyte progenitor cells in serum-free cultures initiated with CD34+ cells.
Authors:
Sigurjonsson, Olafur Eysteinn; Gudmundsson, Kristbjorn Orri; Haraldsdottir, Vilhelmina; Rafnar, Thorunn; Gudmundsson, Sveinn
Citation:
J. Hematother. Stem Cell Res. 2002, 11(2):389-400
Issue Date:
2-Apr-2002
Abstract:
Megakaryocytopoiesis involves proliferation and maturation of committed precursors that increase their size by polyploidy, a process that is believed to be critical for the efficient production and release of platelets. Thrombopoietin has been shown to act on proliferation, maturation, and survival pathways in megakaryocytopoiesis. Less is known about the role of Flt3/Flk-2-ligand in this development. Apoptosis has an important role in hematopoiesis in general. It has been shown to have an effect on senescent megakaryocytes but not megakaryocyte progenitor cells. In this study, a serum-free culture model was developed, differentiating bone marrow CD34(+) hematopoietic stem cells into megakaryocytes, using thrombopoietin and Flt3/Flk-2-ligand. The model was used to study the effect of these growth factors on expansion of megakaryocyte progenitor cells, differentiation of megakaryocytes, and ploidy. Our results demonstrate that bone marrow CD34(+) cells cultured with thrombopoietin and Flt3/Flk-2-ligand show a lower developmental rate into MK cells compared to cells cultured with thrombopoietin alone. Cells cultured with thrombopoietin and Flt3/Flk-2-ligand expressed less CD41, the ploidy level was lower, and they appeared less mature. On the other hand, the cells showed up to 10-fold increase in cell numbers compared to five-fold increase when cultured with thrombopoietin alone. These results suggest that Flt3/Flk-2-ligand in synergy with thrombopoietin may slow down megakaryocyte development by causing increased proliferation of megakaryocyte progenitor cells.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1089/152581602753658574

Full metadata record

DC FieldValue Language
dc.contributor.authorSigurjonsson, Olafur Eysteinn-
dc.contributor.authorGudmundsson, Kristbjorn Orri-
dc.contributor.authorHaraldsdottir, Vilhelmina-
dc.contributor.authorRafnar, Thorunn-
dc.contributor.authorGudmundsson, Sveinn-
dc.date.accessioned2008-07-01T11:23:39Z-
dc.date.available2008-07-01T11:23:39Z-
dc.date.issued2002-04-02-
dc.date.submitted2008-07-01-
dc.identifier.citationJ. Hematother. Stem Cell Res. 2002, 11(2):389-400en
dc.identifier.issn1525-8165-
dc.identifier.pmid11983110-
dc.identifier.doi10.1089/152581602753658574-
dc.identifier.urihttp://hdl.handle.net/2336/30755-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractMegakaryocytopoiesis involves proliferation and maturation of committed precursors that increase their size by polyploidy, a process that is believed to be critical for the efficient production and release of platelets. Thrombopoietin has been shown to act on proliferation, maturation, and survival pathways in megakaryocytopoiesis. Less is known about the role of Flt3/Flk-2-ligand in this development. Apoptosis has an important role in hematopoiesis in general. It has been shown to have an effect on senescent megakaryocytes but not megakaryocyte progenitor cells. In this study, a serum-free culture model was developed, differentiating bone marrow CD34(+) hematopoietic stem cells into megakaryocytes, using thrombopoietin and Flt3/Flk-2-ligand. The model was used to study the effect of these growth factors on expansion of megakaryocyte progenitor cells, differentiation of megakaryocytes, and ploidy. Our results demonstrate that bone marrow CD34(+) cells cultured with thrombopoietin and Flt3/Flk-2-ligand show a lower developmental rate into MK cells compared to cells cultured with thrombopoietin alone. Cells cultured with thrombopoietin and Flt3/Flk-2-ligand expressed less CD41, the ploidy level was lower, and they appeared less mature. On the other hand, the cells showed up to 10-fold increase in cell numbers compared to five-fold increase when cultured with thrombopoietin alone. These results suggest that Flt3/Flk-2-ligand in synergy with thrombopoietin may slow down megakaryocyte development by causing increased proliferation of megakaryocyte progenitor cells.en
dc.language.isoenen
dc.publisherMary Ann Liebert, Inc.en
dc.relation.urlhttp://dx.doi.org/10.1089/152581602753658574en
dc.subject.meshAntigens, CD34en
dc.subject.meshBone Marrow Cellsen
dc.subject.meshCell Counten
dc.subject.meshCell Culture Techniquesen
dc.subject.meshCell Differentiationen
dc.subject.meshCulture Media, Serum-Freeen
dc.subject.meshDrug Synergismen
dc.subject.meshErythroid Progenitor Cellsen
dc.subject.meshHematopoiesisen
dc.subject.meshHumansen
dc.subject.meshMegakaryocytesen
dc.subject.meshMembrane Proteinsen
dc.subject.meshProto-Oncogene Proteinsen
dc.subject.meshReceptor Protein-Tyrosine Kinasesen
dc.subject.meshThrombopoietinen
dc.subject.meshfms-Like Tyrosine Kinase 3en
dc.titleFlt3/Flk-2-ligand in synergy with thrombopoietin delays megakaryocyte development and increases the numbers of megakaryocyte progenitor cells in serum-free cultures initiated with CD34+ cells.en
dc.typeArticleen
dc.contributor.departmentThe Blood Bank, Department of Basic Research, Landspitali-University Hospital, 101 Reykjavík, Iceland. oes@landspitali.isen
dc.identifier.journalJournal of hematotherapy & stem cell researchen

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