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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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Hattori K,Heissig B,Wu Y,Dias S,Tejada R,Ferris B,Hicklin DJ,Zhu Z,Bohlen P,Witte L,Hendrikx J,Hackett NR,Crystal RG,Moore MA,Werb Z,Lyden D,Rafii S

doi

10.1038/nm740

keywords:

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

841-9

issue

8

eissn

1078-8956

issn

1546-170X

pii

nm740

journal_volume

8

pub_type

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