CD14 positive cells accelerate hematopoietic stem cell engraftment

The improvement of hematopoietic stem and progenitor cell (HSPC) engraftment remains a high-priority goal when limited cell doses are available, such as in cord blood (CB) transplantation and HSC gene therapy. We observed that monocytes are highly effective at improving the engraftment of both CB-CD34(+) and lentivirus-transfected CD34(+) cells in a xenogeneic model of HSC transplantation. Moreover, monocytes, in particular the CD14(+)CD16(-) classical subset, in co-culture systems increase survival and stemness of CB-CD34(+) cells. Both soluble factors and direct-cell contact interactions, such as JAG/NOTCH and COX-2/PGE2 pathways, are critically involved in the HSC-monocyte crosstalk. Our results indicate that the infusion of monocytes improves engraftment when cell dose is a limiting factor.