Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+ stem cells from bone-marrow microenvironment View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2002-07-01

AUTHORS

Koichi Hattori, Beate Heissig, Yan Wu, Sergio Dias, Rafael Tejada, Barbara Ferris, Daniel J. Hicklin, Zhenping Zhu, Peter Bohlen, Larry Witte, Jan Hendrikx, Neil R. Hackett, Ronald G. Crystal, Malcolm A.S. Moore, Zena Werb, David Lyden, Shahin Rafii

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. More... »

PAGES

841-849

Journal

TITLE

Nature Medicine

ISSUE

8

VOLUME

8

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nm740

    DOI

    http://dx.doi.org/10.1038/nm740

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1011527446

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12091880


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