DIRECT GROWTH SUPPRESSION OF MYELOID BONE-MARROW PROGENITOR CELLS BUTNOT CORD-BLOOD PROGENITORS BY HUMAN CYTOMEGALOVIRUS IN-VITRO

Recently, considerable interest has arisen as to use cord blood (CB) a s a source of hematopoietic stem cells for allogenic transplantation w hen bone marrow (BM) from a familial HLA-matched donor is not availabl e. 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. Th erefore, 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 granulocy te-macrophage colony-stimulating factor (CSF), granulocyte-CSF, macrop hage-CSF, interleukin-3 (IL-3) and the combination of IL-3 and stem ce ll 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 s uppressed, 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 obse rved in infected cells. Cell cyclus examination of BM and CB CD34(+) c ells revealed that 25.7% of BM progenitors were in S + G(2)/M phase wh eras only 10.7% of the CB progenitors. Thus, a clinical isolate of HCM V directly inhibited the proliferation of myeloid BM progenitors in vi tro wheras CB progenitors were not affected, This difference in the su sceptibility of CB and BM cells to HCMV may partly be caused by the sl ow cycling rate of naive CB progenitors compared to BM progenitors at the time of infection. (C) 1996 by The American Society of Hematology.