Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antimetabolites, Antineoplastic
  • Cell Separation
  • Cell Transplantation
  • Chemotaxis
  • Female
  • Fluorouracil
  • Humans
  • Male
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred Strains
  • Placenta Growth Factor
  • Receptors, Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Transplantation Chimera
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor Receptor-1

MeSH Major

  • Hematopoiesis
  • Hematopoietic Stem Cells
  • Pregnancy Proteins
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases

abstract

  • The mechanism by which angiogenic factors recruit bone marrow (BM)-derived quiescent endothelial and hematopoietic stem cells (HSCs) is not known. Here, we report that functional vascular endothelial growth factor receptor-1 (VEGFR1) is expressed on human CD34(+) and mouse Lin(-)Sca-1(+)c-Kit(+) BM-repopulating stem cells, conveying signals for recruitment of HSCs and reconstitution of hematopoiesis. Inhibition of VEGFR1, but not VEGFR2, blocked HSC cell cycling, differentiation and hematopoietic recovery after BM suppression, resulting in the demise of the treated mice. Placental growth factor (PlGF), which signals through VEGFR1, restored early and late phases of hematopoiesis following BM suppression. PlGF enhanced early phases of BM recovery directly through rapid chemotaxis of VEGFR1(+) BM-repopulating and progenitor cells. The late phase of hematopoietic recovery was driven by PlGF-induced upregulation of matrix metalloproteinase-9, mediating the release of soluble Kit ligand. Thus, PlGF promotes recruitment of VEGFR1(+) HSCs from a quiescent to a proliferative BM microenvironment, favoring differentiation, mobilization and reconstitution of hematopoiesis.

publication date

  • August 2002

has subject area

  • Animals
  • Antimetabolites, Antineoplastic
  • Cell Separation
  • Cell Transplantation
  • Chemotaxis
  • Female
  • Fluorouracil
  • Hematopoiesis
  • Hematopoietic Stem Cells
  • Humans
  • Male
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred Strains
  • Placenta Growth Factor
  • Pregnancy Proteins
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Transplantation Chimera
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor Receptor-1

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2779715

Digital Object Identifier (DOI)

  • 10.1038/nm740

PubMed ID

  • 12091880

Additional Document Info

start page

  • 841

end page

  • 849

volume

  • 8

number

  • 8