Faculty Research 1990 - 1999

Title

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

Document Type

Article

Publication Date

1999

Keywords

Antibodies, Antigens-CD34: an, im, Antigens-Differentiation: an, Chemokines-CXC: ph, Chemotaxis, Colony-Forming-Units-Assay, Fetal-Blood, Hematopoietic-Stem-Cell-Mobilization, Hematopoietic-Stem-Cell-Transplantation, Hematopoietic-Stem-Cells: ph, Human, Interleukin-6, Mice, Mice-Inbred-NOD, Mice-Knockout, Mice-SCID, NAD+-Nucleosidase: an, Receptors-CXCR4: bi, im, ph, Stem-Cell-Factor, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Tetradecanoylphorbol-Acetate, Up-Regulation-(Physiology)

JAX Source

Science 1999 Feb 5;283(5403):845-8

Grant

A130389

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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