In vitro expansion of long-term repopulating hematopoietic stem cells in the presence of immobilized Jagged-1 and early acting cytokines

Cell Biology International
Zsuzsanna KertészFerenc Uher

Abstract

There is an increasing body of evidence that suggests that genes involved in cell fate decisions and pattern formation during development also play a key role in the continuous cell fate decisions made by adult tissue stem cells. Here we show that prolonged in vitro culture (14 days) of murine bone marrow lineage negative cells in medium supplemented with three early acting cytokines (stem cell factor, Flk-2/Flt-3 ligand, thrombopoietin) and with immobilized Notch ligand, Jagged-1, resulted in robust expansion of serially transplantable hematopoietic stem cells with long-term repopulating ability. We found that the absolute number of marrow cells was increased approximately 8 to 14-fold in all cultures containing recombinant growth factors. However, the frequency of high quality stem cells was markedly reduced at the same time, except in cultures containing growth factors and Jagged-1-coated Sepharose-4B beads. The absolute number of hematopoietic cells with long-term repopulating ability was increased approximately 10 to 20-fold in the presence of multivalent Notch ligand. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic stem cell fate and to a ...Continue Reading

Citations

Sep 14, 2010·Expert Review of Hematology·Colleen DelaneyMary J Laughlin
Mar 7, 2009·Biologicals : Journal of the International Association of Biological Standardization·Hyun-Joo LeeDong-Ku Kim
Aug 30, 2008·Current Opinion in Biotechnology·Shara M DellatoreWilliam M Miller
Mar 26, 2016·Annals of the New York Academy of Sciences·Dirk KanzClaudia Lengerke
Jun 17, 2015·Journal of Nanobiotechnology·Cristian T MateaLucian-Constantin Mocan

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