Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4

Stem cell homing and repopulation are not well understood. The chemokine st romal cell-derived factor-1 (SDF-1) and its receptor CXCR4 were found to be critical for murine bone marrow engraftment by human severe combined immun odeficient (SCID) repopulating stem cells. Treatment of human cells with an tibodies to CXCR4 prevented engraftment. In vitro CXCR4-dependent migration to SDF-1 of CD34(+)CD38(-/low) cells correlated with in vivo engraftment a nd stem cell function. Stem cell factor and interleukin-6 induced CXCR4 exp ression on CD34(+) cells, which potentiated migration to SDF-1 and engraftm ent in primary and secondary transplanted mice. Thus, up-regulation of CXCR 4 expression may be useful for improving engraftment of repopulating stem c ells in clinical transplantation.