Augmentation of donor bone marrow engraftment in histoincompatible murine
recipients by granulocyte/macrophage colony-stimulating factor
BR Blazar, MB Widmer, CC Soderling, DL Urdal, S Gillis, LL Robison and DA Vallera
Department of Pediatrics, University of Minnesota Hospital, Minneapolis
55455.
T cell depletion of donor bone marrow can prevent graft v host disease
(GVHD) in human and murine marrow graft recipients. However, engraftment in
the recipient may be compromised as a consequence of donor marrow T cell
depletion. The effect of recombinant murine granulocyte/macrophage
colony-stimulating factor (rmu GM-CSF) on engraftment and hematologic
reconstitution was evaluated in a murine allogeneic bone marrow
transplantation (BMT) model involving T cell depletion of marrow. Before
transplantation into irradiated mice differing at major and minor
histocompatibility loci, rmu GM-CSF was preincubated with T cell-depleted
donor marrow. When low degrees of engraftment were noted in control
recipients, treatment of donor marrow with high concentrations of rmu
GM-CSF led to enhanced engraftment. Ex vivo donor graft incubation with rmu
GM-CSF or a single in vivo injection of rmu GM-CSF were both effective
means of promoting engraftment. When the engraftment rate in control
recipients was high, rmu GM-CSF did not have an identifiable effect. Only
slight increases in hematologic recovery were detected regardless of the
rate of engraftment. Neither post-BMT survival nor marrow stem cell
capacity was affected by rmu GM-CSF incubation. Furthermore, growth factor
administration did not have a significant effect on the incidence of GVHD
in recipients of non-T cell-depleted bone marrow splenocyte preparations.
In vitro natural killer-mediated target cell lysis was not altered by
incubation of effector cells with rmu GM-CSF. These results demonstrate the
potential of ex vivo rmu GM-CSF treatment of donor marrow to facilitate
engraftment across extensive histo- compatibility barriers.
Volume 71,
Issue 2,
pp. 320-328,
02/01/1988
Copyright © 1988 by The American Society of Hematology