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

  title={Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4.},
  author={Amnon Peled and Isabelle Petit and Orit Kollet and Michal Magid and Tatyana Ponomaryov and Tamara V. Byk and Arnon Nagler and Herzl Ben‐Hur and Ariel Many and Leonard Shultz and Ofer Lider and Ronen Alon and Dov Zipori and Tsvee Lapidot},
  volume={283 5403},
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… 

CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice.

The findings demonstrated the importance of the SDF-1/CX CR4 axis in the regulation of in vivo motility and development of human AML stem cells and identified CXCR4 neutralization as a potential treatment for AML.

Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation.

The results suggest CXCR4 overexpression for improved definitive human stem cell motility, retention, and multilineage repopulation, which could be beneficial for in vivo navigation and expansion of hematopoietic progenitors.

CXCR 4 Regulates Migration and Development of Human Acute Myelogenous Leukemia Stem Cells in Transplanted NOD / SCID Mice

The findings demonstrated the importance of the SDF-1/CX CR4 axis in the regulation of in vivo motility and development of human AML stem cells and identified CXCR4 neutralization as a potential treatment for AML.

Mechanism of Human Stem Cell Migration and Repopulation of NOD/SCID and B2mnull NOD/SCID Mice

  • T. Lapidot
  • Biology
    Annals of the New York Academy of Sciences
  • 2001
A major role is suggested for SDF‐1/CXCR4 interactions in murine stem cell homing from the fetal liver into the bone marrow and its repopulation during development and in vivo homing and repopulating in transplanted immune‐deficient mice.

The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2mnull mice

The essential roles of the chemokine SDF-1 and its receptor CXCR4 which mediate and regulate stem cell homing and repopulation will be discussed.

Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6, and soluble IL-6 receptor.

The present study may provide a novel culture method for the expansion of human transplantable hematopoietic stem cells suitable for clinical applications.

Chemokine-mobilized adult stem cells; defining a better hematopoietic graft

In mice, the HSC and progenitor cells (HPC) mobilized by the CXCR2 receptor agonist GROβ can be harvested within minutes of administration and show significantly lower levels of apoptosis, enhanced homing to marrow, expression of more activated integrin receptors and superior repopulation kinetics and more competitive engraftment than the equivalent cells mobilized by G-CSF.

Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4

The development of small-molecule CXCR4 and VLA-4 inhibitors are discussed and how they may improve the utility and convenience of peripheral blood stem cell transplantation.

Short-term culture of umbilical cord blood-derived CD34 cells enhances engraftment into NOD/SCID mice through increased CXCR4 expression.

It is suggested that increased cell surface expression of CXCR4 on CD34(+) cells improved the engraftment of human umbilical CB cells into bone marrow through enhanced homing activity.



Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice.

Severe combined immunodeficient mice transplanted with human bone marrow were treated with human mast cell growth factor, a fusion of interleukin-3 and granulocyte-macrophage colony-stimulating factor (PIXY321), or both, and this system allows the detection of immature human cells, identification of the growth factors that regulate them, and the establishment of animal models of human hematopoietic diseases.

Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy

A novel human hematopoietic cell, the SCID–repopulating cell (SRC), a cell more primitive than most LTC–ICs and CFCs, that is capable of multilineage repopulation of the bone marrow of nonobese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice).

Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1

It is shown that the chemokine PBSF/SDF-1 has several essential functions in development, including B-cell lymphopoiesis and bone-marrow myelopoiedis and a cardiac ventricular septal defect.

Sustained human hematopoiesis in immunodeficient mice by cotransplantation of marrow stroma expressing human interleukin-3: analysis of gene transduction of long-lived progenitors.

A novel cotransplantation system in which gene-transduced human CD34+ progenitor cells are transplanted into immunodeficient mice together with primary human bone marrow stromal cells engineered to produce human interleukin-3 (IL-3).

The biology of hematopoietic stem cells.

The subsets of HSC that give rise to short-term vs long-term multilineage reconstitution can be separated by phenotype, demonstrating that the fates of H SC are intrinsically determined.

The Chemokine SDF-1 Is a Chemoattractant for Human CD34+ Hematopoietic Progenitor Cells and Provides a New Mechanism to Explain the Mobilization of CD34+ Progenitors to Peripheral Blood

Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first

Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice.

The higher levels of human CD4+ T cells and the normalization of the CD4:CD8 ratio that are observed in human PBMC-engrafted NOD/LtSz-scid/scid B2m(null) mice suggest that this system may be an excellent model for studies of HIV pathogenesis.

Quantitation, mobilization, and clinical use of long-term culture-initiating cells in blood cell autografts.

The long-term culture-initiating cell is a very primitive hematopoietic with unique phenotypic feature and the potential role and significance of these cells in peripheral blood cell autografts is discussed.

Disturbed CD4+ T Cell Homeostasis and In Vitro HIV-1 Susceptibility in Transgenic Mice Expressing T Cell Line–tropic HIV-1 Receptors

A hypothetical model is proposed in which the dual function of CXCR4 in HIV-1 infection and in lymphocyte trafficking may cooperatively induce progressive HIV- 1 infection and CD4+ T cell decline in patients.

The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function.

Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency.