Mpl ligand (MGDF) alone and in combination with stem cell factor (SCF) promotes proliferation and survival of human megakaryocyte, erythroid and granulocyte/macrophage progenitors

Stem Cells
J E RaskoC G Begley

Abstract

We examined cytokine-stimulated proliferation and survival of human megakaryocyte progenitor cells. We used a reliable, immunoenzymatic method of labeling CD41a-, CD42b-stained megakaryocytes in intact agar cultures to specifically identify and enumerate all megakaryocyte-containing colonies. We examined a previously defined population of cells enriched for megakaryocyte progenitors that coexpress CD34 and the megakaryocyte/platelet marker CD61. These CD34+61+ cells displayed clonogenicity of approximately 30% and contained myeloid, erythroid and megakaryocyte progenitor cells. With single CD34+61+ cells, megakaryocyte growth and development factor ([MGDF], also known as mpl-ligand or thrombopoietin) stimulated 9% of cells to complete their first cell division by day 2 (versus 21% with stem cell factor [SCF], or 13% with interleukin 3 alone). MGDF showed an additive effect with SCF and interleukin 3 to increase this number at least twofold. In purified CD34+61+ cells, MGDF stimulated the survival of megakaryocyte-colony forming cells (CFC) when addition of other proliferative factors was delayed for 5, 10 and 15 days (all p < 0.0001 versus saline control). MGDF also promoted survival of BFU-E and granulocyte-macrophage-CFC for ...Continue Reading

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Citations

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