Ex vivo expansion with stem cell factor and interleukin-11 augments both short-term recovery posttransplant and the ability to serially transplant marrow.
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.
Holyoake
T L
TL
Cancer Research Campaign Beatson Laboratories, Beaston Institute for Cancer Research, Glasgow, Scotland.
Freshney
M G
MG
McNair
L
L
Parker
A N
AN
McKay
P J
PJ
Steward
W P
WP
Fitzsimons
E
E
Graham
G J
GJ
Pragnell
I B
IB
D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000637:transplantation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology
D017077:Culture Media, Conditioned; D016298:Hematopoietic Cell Growth Factors; D017370:Interleukin-11; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor