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Ex vivo incubation with growth factors enhances the engraftment of fetal
hematopoietic cells transplanted in sheep fetuses
ED Zanjani, JL Ascensao, MR Harrison and M Tavassoli
Department of Veterans Affairs Medical Center, Reno, NV 89520.
Hematopoietic stem cells (HSC) transplanted in utero are in competition
with endogenous HSC; thus, ultimately the graft constitutes a relatively
small fraction of total HSC pool. To enhance the engraftment of donor cells
in sheep fetuses, we preincubated these cells, ex vivo, for 16 hours at 37
degrees C with the conditioned medium from phytohemagglutinin-stimulated
lymphocytes (PHA-LCM) before in utero transplantation. PHA-LCM is a rich
source of hematopoietic growth factors in sheep. Subsequent engraftment was
significantly higher in cells preincubated with PHA-LCM compared with fresh
cells or those incubated with control medium only. This was reflected in
all markers of the donor cells (hemoglobin type, karyotype, and progenitor
cell assays). Brief ex vivo incubation with PHA-LCM also increased
viability of all marrow cells as well as total numbers of progenitors.
Similar enhancement of engraftment was also noted in monkeys after a brief
preincubation of donor cells with interleukin-3 (IL-3) and granulocyte-
macrophage colony-stimulating factor (GM-CSF). We conclude that brief (16
hours) ex vivo incubation of donor cells with a source of such growth
factors as IL-3 and GM-CSF enhances the subsequent engraftment of
transplanted cells.
Volume 79,
Issue 11,
pp. 3045-3049,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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