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FLT3 ligand preserves the ability of human CD34+ progenitors to sustain
long-term hematopoiesis in immune-deficient mice after ex vivo
retroviral-mediated transduction
MA Dao, CH Hannum, DB Kohn and JA Nolta
Division of Research Immunology/Bone Marrow Transplantation, Childrens
Hospital Los Angeles, CA 90027, USA.
Stromal support is required during retroviral-mediated transduction of
human bone marrow-derived CD34+ cells to maintain the clonogenicity of the
primitive progenitors. We hypothesized that the cytokine FLT3 ligand (FL)
might be able to replace the maintenance role provided by the stroma. CD34+
progenitors from human bone marrow were transduced by the retroviral vector
LN with the cytokines interleukin-3 (IL-3), IL-6, and stem cell factor
(SCF) present in all cultures. Transductions were performed with or without
stromal support and with or without the inclusion of 100 U/mL FL. No
significant increase in gene transfer into colony-forming cells was
obtained by the addition of FL to the cultures. Transduction and survival
of more primitive human hematopoietic cells was determined by growth in
immune-deficient mice for 7 to 8 months. Human myeloid cells, T
lymphocytes, and colony- forming progenitors were recovered from the marrow
of mice that had received human cells transduced on stroma or in suspension
culture with IL-3, IL-6, SCF, and FL, but not with IL-3, IL-6, and SCF
alone. LN provirus was detected by polymerase chain reaction in the marrow
recovered from 9 of 10 mice transplanted with human CD34+ cells transduced
with stromal support, 5 of 11 mice that received human cells transduced in
suspension culture with FL, but none of the 10 mice that received human
cells transduced in suspension culture without FL We conclude that FLT3
ligand, in conjunction with IL-3, IL-6, and SCF, preserves the generative
capacity of primitive human hematopoietic cells during in vitro
transductions in suspension culture.
Volume 89,
Issue 2,
pp. 446-456,
01/15/1997
Copyright © 1997 by The American Society of Hematology
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