Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Angiopoietin-1
  • Animals
  • Bone Marrow
  • Cell Count
  • Chemokine CXCL12
  • Colony-Forming Units Assay
  • Genetic Vectors
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Spleen
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

MeSH Major

  • Chemokines, CXC
  • Chemotaxis
  • Endothelial Growth Factors
  • Endothelium, Vascular
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells
  • Leukocytosis
  • Lymphokines
  • Membrane Glycoproteins
  • Neovascularization, Pathologic
  • Splenomegaly
  • Stem Cells

abstract

  • The chemokine stroma-derived factor-1 (SDF-1) is produced within the bone marrow and mediates chemokinesis and chemotaxis on a variety of cell types that express the CXCR4 receptor. SDF-1-responsive cell types include monocytes and macrophages, B and T lymphocytes, platelets and megakaryocytes, and CD34+ cells, including both hematopoietic progenitors and stem cells. We have used intravenous injection of a replication-incompetent adenovector expressing the SDF-1 gene to elevate serum levels of SDF-1 in Balb/c and SCID mice. Within 3 to 5 days there was a marked leukocytosis, predominantly involving monocytes, and a three-fold increase in platelets. In addition, AdSDF-1 mobilized CFU-GM, CFU-s, and cells with long-term repopulating potential. We have identified a bone marrow-derived, circulating endothelial stem cell characterized by expression of the VEGFR2 (Flk-1/KDR). This cell exhibits a chemotactic and chemokinetic response to SDF-1 and VEGF. We have elevated serum levels of VEGF165 using intravenous adenovector gene delivery and compared this to an adenovector expressing angiopoietin-1 alone or in combination with VEGF. VEGF elevation was associated with rapid mobilization of hematopoietic stem and progenitor cells and a population of Flk-1-positive endothelial progenitors. In contrast angiopoietin induced a delayed mobilization of endothelial and hematopoietic progenitors. The combination of VEGF and angiopoietin produced a more prolonged elevation of these progenitors in the circulation with increased proliferation of capillaries and expansion of sinusoidal spaces in the marrow.

publication date

  • June 2001

has subject area

  • Adenoviridae
  • Angiopoietin-1
  • Animals
  • Bone Marrow
  • Cell Count
  • Chemokine CXCL12
  • Chemokines, CXC
  • Chemotaxis
  • Colony-Forming Units Assay
  • Endothelial Growth Factors
  • Endothelium, Vascular
  • Genetic Vectors
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells
  • Leukocytosis
  • Lymphokines
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Neovascularization, Pathologic
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Spleen
  • Splenomegaly
  • Stem Cells
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 11458524

Additional Document Info

start page

  • 36

end page

  • 45; discussion 45-7

volume

  • 938