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Ex vivo expansion with stem cell factor and interleukin-11 augments both
short-term recovery posttransplant and the ability to serially transplant
marrow
TL Holyoake, MG Freshney, L McNair, AN Parker, PJ McKay, WP Steward, E Fitzsimons, GJ Graham and IB Pragnell
Cancer Research Campaign Beatson Laboratories, Beaston Institute for Cancer
Research, Glasgow, Scotland.
The characterization of many cytokines involved in the control of
hematopoiesis has led to intense investigation into their potential use in
ex vivo culture to expand progenitor numbers. We have established the
optimum ex vivo culture conditions that allow substantial amplification of
transient engrafting murine stem cells and which, simultaneously, augment
the ability to sustain serial bone marrow transplantation (BMT). Short-term
incubation of unfractionated BM cells in liquid culture with stem cell
factor (SCF) and interleukin-11 (IL- 11) produced a 50-fold amplification
of clonogenic multipotential progenitors (CFU-A). Following such ex vivo
expansion, substantially fewer cells were required to rescue lethally
irradiated mice. When transplanted in cell doses above threshold for
engraftment, BM cells expanded ex vivo resulted in significantly more rapid
hematopoietic recovery. In a serial transplantation model, unmanipulated BM
was only able to consistently sustain secondary BMT recipients, but BM
expanded ex vivo has sustained quaternary BMT recipients that remain alive
and well more than 140 days after 4th degree BMT. These results show
augmentation of both short-term recovery posttransplant and the ability to
serially transplant marrow by preincubation in culture with SCF and IL-11.
Volume 87,
Issue 11,
pp. 4589-4595,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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