These authors contributed equally to this work.
In vitro expansion of long-term repopulating hematopoietic stem cells in the presence of immobilized Jagged-1 and early acting cytokines
Article first published online: 2 JAN 2013
© The Author(s) Journal compilation © 2006 International Federation for Cell Biology
Cell Biology International
Volume 30, Issue 5, pages 401–405, May 2006
How to Cite
Kertész, Z., Vas, V., Kiss, J., Urbán, V. S., Pozsonyi, É., Kozma, A., Pálóczi, K. and Uher, F. (2006), In vitro expansion of long-term repopulating hematopoietic stem cells in the presence of immobilized Jagged-1 and early acting cytokines. Cell Biology International, 30: 401–405. doi: 10.1016/j.cellbi.2005.11.011
- Issue published online: 2 JAN 2013
- Article first published online: 2 JAN 2013
- Received 4 April 2005, revised 12 August 2005, accepted 10 November 2005
- Long-term repopulating ability stem cells;
- Notch signaling;
- Serial BM transplantation
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 ∼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 ∼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 potential role for Notch ligand in increasing cell numbers in clinical stem cell transplantation.