Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment Journal Article


Authors: Hattori, K.; Heissig, B.; Wu, Y.; Dias, S.; Tejada, R.; Ferris, B.; Hicklin, D. J.; Zhu, Z. P.; Bohlen, P.; Witte, L.; Hendrikx, J.; Hackett, N. R.; Crystal, R. G.; Moore, M. A. S.; Werb, Z.; Lyden, D.; Rafii, S.
Article Title: Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment
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.
Keywords: mice; tyrosine kinase; cells; endothelial-cells; inhibition; tumor angiogenesis; progenitor; mobilization; factor vegf; factor receptor-1; flt-1
Journal Title: Nature Medicine
Volume: 8
Issue: 8
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2002-08-01
Start Page: 841
End Page: 849
Language: English
ACCESSION: WOS:000177200900030
DOI: 10.1038/740
PROVIDER: wos
PMCID: PMC2779715
PUBMED: 12091880
Notes: Article -- Source: Wos
Altmetric Score
MSK Authors
  1. David C Lyden
    84 Lyden
  2. Malcolm A S Moore
    428 Moore