Dependence of Human Stem Cell Engraftment and Repopulation of NOD/SCID Mice on CXCR4

TLDR

Stem cell homing and repopulation are poorly understood, but the SDF‑1/CXCR4 axis has been shown to be critical for murine bone marrow engraftment by human SCID repopulating stem cells. Up‑regulating CXCR4 expression may improve engraftment of repopulating stem cells in clinical transplantation. Antibody blockade of CXCR4 abrogated engraftment, while CXCR4‑dependent migration of CD34+CD38−/low cells to SDF‑1 correlated with in vivo engraftment and stem cell function, and cytokine‑induced CXCR4 expression on CD34+ cells enhanced migration to SDF‑1 and engraftment in primary and secondary transplants.

Abstract

Stem cell homing and repopulation are not well understood. The chemokine stromal cell–derived factor-1 (SDF-1) and its receptor CXCR4 were found to be critical for murine bone marrow engraftment by human severe combined immunodeficient (SCID) repopulating stem cells. Treatment of human cells with antibodies to CXCR4 prevented engraftment. In vitro CXCR4-dependent migration to SDF-1 of CD34 + CD38 −/low cells correlated with in vivo engraftment and stem cell function. Stem cell factor and interleukin-6 induced CXCR4 expression on CD34 + cells, which potentiated migration to SDF-1 and engraftment in primary and secondary transplanted mice. Thus, up-regulation of CXCR4 expression may be useful for improving engraftment of repopulating stem cells in clinical transplantation.