Abstract
Megakaryocyte growth and development factor (MGDF), or thrombopoietin, has received considerable attention as a therapeutic agent for treating thrombocytopenia or for its use in the ex vivo culture of hematopoietic stem cells. MGDF is known to support the growth of a broad spectrum of hematopoietic precursors obtained from adult or neonatal tissues, but its effects on the growth of fetal progenitors and stem cells has not been studied. Human CD38+CD342+ progenitors and CD38−CD342+ cells, a population that contains stem cells, were isolated from midgestation liver and grown under defined conditions with MGDF and various cytokines known to support the growth of primitive hematopoietic precursors. In clonal assays of colony-forming cells (CFCs), MGDF supported the growth of 15–25% of candidate stem cells when combined with granulocyte colony-stimulating factor, granulocytemacrophage colony-stimulating factor (GM-CSF), flk-2/flt3 ligand, or stem cell factor. MGDF was observed to strongly support the early stages of hematopoiesis and expansion of high proliferative potential CFCs. More mature progenitors were expanded nearly 78-fold in 1 wk of culture with MGDF+SCF+GM-CSF. MGDF alone was also found to support the short-term (2 d) survival of CD38−CD342+ high proliferative potential CFCs. The effects of MGDF were more modest on CD38+CD342+ progenitors with only additive increases in colony formation being observed. These findings suggest that MGDF administration in fetuses and neonates may strongly affect the growth and mobilization of primitive hematopoietic progenitors and that MGDF may find use in the ex vivo growth and expansion of fetal stem cells.
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Abbreviations
- CFC:
-
colony-forming cell
- FL:
-
flk-2/flt3 ligand
- G-CSF:
-
granulocyte colony-stimulating factor
- GM-CSF:
-
granulocyte-macrophage colony-stimulating factor
- HPP:
-
high proliferative potential
- LPP:
-
low proliferative potential
- MGDF:
-
megakaryocyte growth and development factor
- SCF:
-
stem cell factor
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Acknowledgements
We thank William Hyun and Jane W. Gordon, from the Laboratory of Cell Analysis (UCSF), and Suk Park from Ingenex for assistance with cell sorting. We thank Dr. Jae-Hung Shieh (Amgen) for providing cytokines used in this study. We also are indebted to Dr. Yuet Wai Kan for generous support.
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This work was supported in part by National Institutes of Health Grant DK59301 and an Individual Investigator Research grant from the University of California at San Francisco Academic Senate (M.O.M.).
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Muench, M., Bárcena, A. Megakaryocyte Growth and Development Factor Is a Potent Growth Factor for Primitive Hematopoietic Progenitors in the Human Fetus. Pediatr Res 55, 1050–1056 (2004). https://doi.org/10.1203/01.pdr.0000127020.00090.51
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DOI: https://doi.org/10.1203/01.pdr.0000127020.00090.51
