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In vitro expansion of hematopoietic progenitors and maintenance of stem
cells: comparison between FLT3/FLK-2 ligand and KIT ligand
Y Yonemura, H Ku, SD Lyman and M Ogawa
Department of Medicine, Medical University of South Carolina, Charleston
29401-5799, USA.
The effects of FLT3/FLK-2 ligand (FL) and KIT ligand (KL) on in vitro
expansion of hematopoietic stem cells were studied using lineage- negative
(Lin-)Sca-1-positive (Sca-1+) c-kit-positive (c-kit+) marrow cells from
5-fluorouracil (5-FU)-treated mice. As single agents, neither FL nor KL
could effectively support the proliferation of enriched cells in suspension
culture. However, in combination with interleukin-11 (IL-11), both FL and
KL enhanced the production of nucleated cells and progenitors. The kinetics
of stimulation by FL was different from that by KL in that the maximal
expansion by FL of the nucleated cell and progenitor pools required a
longer incubation than with KL. We then tested the reconstituting abilities
of cells cultured for 1, 2, and 3 weeks by transplanting the expanded Ly5.1
cells together with "compromised" marrow cells into lethally irradiated
Ly5.2 mice. Cells that had been expanded with either cytokine combination
were able to maintain the reconstituting ability of the original cells.
Only cells that had been incubated with KL and IL-11 for 21 days had less
reconstituting ability than fresh marrow cells. These results indicate that
there can be significant expansion of progenitors in vitro without
compromising the reconstituting ability of stem cells. Addition of IL-3 to
permissive cytokine combinations significantly reduced the ability of
cultured cells to reconstitute the hematopoiesis of irradiated hosts. These
observations should provide a basis for a rational approach to designing
cytokine combinations for in vitro expansion of hematopoietic stem cells.
Volume 89,
Issue 6,
pp. 1915-1921,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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