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

Publication Type	Academic Article
Authors	Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin D, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hackett N, Crystal R, Moore M, Werb Z, Lyden D, Rafii S
Journal	Nat Med
Volume	8
Issue	8
Pagination	841-9
Date Published	07/01/2002
ISSN	1078-8956
Keywords	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.
DOI	10.1038/nm740
PubMed ID	12091880
PubMed Central ID	PMC2779715