Direct growth suppression of myeloid bone marrow progenitor cells but not
cord blood progenitors by human cytomegalovirus in vitro
M Holberg-Petersen, H Rollag, S Beck, I Overli, G Tjonnfjord, TG Abrahamsen, M Degre and K Hestdal
Department of Pediatric Research, Rikshospitalet, University of Oslo,
Norway.
Recently, considerable interest has arisen as to use cord blood (CB) as a
source of hematopoietic stem cells for allogenic transplantation when bone
marrow (BM) from a familial HLA-matched donor is not available. Because
human cytomegalovirus (HCMV) has been shown to inhibit the proliferation of
BM progenitors in vitro, it was important to examine whether similar effect
could be observed in HCMV-infected CB cells. Therefore, the effect of HCMV
challenge on the proliferation of myeloid progenitors from BM and CB was
compared using both mononuclear cells (MNC) and purified CD34+ cells. A
clinical isolate of HCMV inhibited the colony formation of myeloid BM
progenitors responsive to granulocyte-macrophage colony-stimulating factor
(CSF), granulocyte- CSF, macrophage-CSF, interleukin-3 (IL-3) and the
combination of IL-3 and stem cell factor (SCF). In contrast, colony growth
of CB progenitors was not affected. In addition, HCMV inhibited directly
the growth of purified BM CD34+ cells responsive to IL-3 and SCF in single
cell assay by 40%, wheras the growth of CD34+ progenitors obtained from CB
was not suppressed. The HCMV lower matrix structural protein pp65 and HCMV
DNA were detected in both CB and BM CD34+ cells after in vitro challenge.
However, neither immediate early (IE)-mRNA nor IE proteins were observed in
infected cells. Cell cyclus examination of BM and CB CD34+ cells revealed
that 25.7% of BM progenitors were in S + G2/ M phase wheras only 10.7% of
the CB progenitors. Thus, a clinical isolate of HCMV directly inhibited the
proliferation of myeloid BM progenitors in vitro wheras CB progenitors were
not affected. This difference in the susceptibility of CB and BM cells to
HCMV may partly be caused by the slow cycling rate of naive CB progenitors
compared to BM progenitors at the time of infection.
Volume 88,
Issue 7,
pp. 2510-2516,
10/01/1996
Copyright © 1996 by The American Society of Hematology
