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

Science. 1999 Feb 5;283(5403):845-8. doi: 10.1126/science.283.5403.845.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Animals
  • Antibodies
  • Antigens, CD*
  • Antigens, CD34 / analysis
  • Antigens, CD34 / immunology
  • Antigens, Differentiation / analysis
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology
  • Chemokines, CXC / physiology*
  • Chemotaxis
  • Colony-Forming Units Assay
  • Fetal Blood
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Interleukin-6 / pharmacology
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • NAD+ Nucleosidase / analysis
  • Receptors, CXCR4 / biosynthesis
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / physiology*
  • Stem Cell Factor / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Up-Regulation

Substances

  • Antibodies
  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Interleukin-6
  • Membrane Glycoproteins
  • Receptors, CXCR4
  • Stem Cell Factor
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • Cd38 protein, mouse
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1
  • Tetradecanoylphorbol Acetate