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

Amnon Peled, Isabelle Petit(Weizmann Institute of Science), Órit Kollet(Weizmann Institute of Science), Michal Magid(Weizmann Institute of Science), Tanya Ponomaryov(Weizmann Institute of Science), Tamara Byk(Weizmann Institute of Science), Arnon Nagler(Hadassah Academic College), Herzl Ben‐Hur(Kaplan Medical Center), Ariel Many(Tel Aviv Sourasky Medical Center), Leonard D. Shultz(Jackson Laboratory), Ofer Lider(Weizmann Institute of Science), R. Alon(Weizmann Institute of Science), Dov Zipori(Weizmann Institute of Science), Tsvee Lapidot(Weizmann Institute of Science)
Science
February 5, 1999
10.1126/science.283.5403.845
Cited by 1,684

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.

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