Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand Journal Article


Authors: Heissig, B.; Hattori, K.; Dias, S.; Friedrich, M.; Ferris, B.; Hackett, N. R.; Crystal, R. G.; Besmer, P.; Lyden, D.; Moore, M. A. S.; Werb, Z.; Rafii, S.
Article Title: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand
Abstract: Stem cells within the bone marrow (BM) exist in a quiescent state or are instructed to differentiate and mobilize to circulation following specific signals. Matrix metalloproteinase-9 (MMP-9), induced in BM cells, releases soluble Kit-ligand (sKitL), permitting the transfer of endothelial and hematopoietic stem cells (HSCs) from the quiescent to proliferative niche. BM ablation induces SDF-1, which upregulates MMP-9 expression, and causes shedding of sKitL and recruitment of c-Kit+ stem/progenitors. In MMP-9-/- mice, release of sKitL and HSC motility are impaired, resulting in failure of hematopoietic recovery and increased mortality, while exogenous sKitL restores hematopoiesis and survival after BM ablation. Release of sKitL by MMP-9 enables BM repopulating cells to translocate to a permissive vascular niche favoring differentiation and reconstitution of the stem/progenitor cell pool.
Keywords: signal transduction; controlled study; protein expression; vascular endothelial growth factor a; recovery of function; fluorouracil; nonhuman; animal cell; animals; mice; mice, knockout; cells, cultured; stem cell factor; bone marrow; gelatinase b; animal experiment; cell differentiation; mice, scid; animalia; endothelium cell; hematopoietic stem cells; cell movement; stem cells; hematopoietic stem cell; cell motility; immunosuppressive agents; chemokines; megakaryocytes; myeloid cells; matrix metalloproteinase 9; vascular endothelial growth factors; endothelial growth factors; chemokines, cxc; male; female; priority journal; article; lymphokines
Journal Title: Cell
Volume: 109
Issue: 5
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2002-05-31
Start Page: 625
End Page: 637
Language: English
DOI: 10.1016/s0092-8674(02)00754-7
PUBMED: 12062105
PROVIDER: scopus
PMCID: PMC2826110
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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  1. Malcolm A S Moore
    549 Moore
  2. Peter Besmer
    115 Besmer