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PMID: 12062105 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand.

Cell ·Vol. 109 ·No. 5 ·2002-05-31 ·Pages 625-37

Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S

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.

MeSH Terms
Animals Bone Marrow/drug effects,enzymology Cell Differentiation/physiology Cell Movement/physiology Cells, Cultured Chemokine CXCL12 Chemokines/pharmacology Chemokines, CXC/pharmacology Endothelial Growth Factors/pharmacology Female Fluorouracil/pharmacology Hematopoietic Stem Cells/cytology,metabolism Immunosuppressive Agents/pharmacology Lymphokines/pharmacology Male Matrix Metalloproteinase 9/deficiency,genetics Megakaryocytes/drug effects,immunology Mice Mice, Knockout Mice, SCID Myeloid Cells/drug effects,immunology Recovery of Function/drug effects,immunology Stem Cell Factor/metabolism,pharmacology Stem Cells/cytology,metabolism Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Chemokine CXCL12 Chemokines Chemokines, CXC Cxcl12 protein, mouse Endothelial Growth Factors Immunosuppressive Agents Lymphokines Stem Cell Factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Matrix Metalloproteinase 9 Fluorouracil
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Heissig Beate
Division of Hematology-Oncology, Cornell University Medical College, New York, NY 10021, USA.
Hattori Koichi
Dias Sergio
Friedrich Matthias
Ferris Barbara
Hackett Neil R
Crystal Ronald G
Besmer Peter
Lyden David
Moore Malcolm A S
Werb Zena
Rafii Shahin
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35 references, click to expand
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/s0092-8674(02)00754-7
Published
2002-05-31
Pages
625-37
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2826110
Subset
IM
Grants
NIAMS NIH HHS · R01 AR046238-06A2 · United States
NHLBI NIH HHS · HL-66592 · United States
NHLBI NIH HHS · HL-67839 · United States
NHLBI NIH HHS · HL-61849 · United States
NCI NIH HHS · P01 CA072006-07 · United States
NHLBI NIH HHS · P01 HL067839 · United States
NCI NIH HHS · CA 72006 · United States
NIAMS NIH HHS · AR 46238 · United States
NHLBI NIH HHS · R01 HL061849 · United States
NCI NIH HHS · CA 75072 · United States
NCI NIH HHS · R01 CA075072-03 · United States
NIAMS NIH HHS · R01 AR046238 · United States
NCI NIH HHS · P01 CA072006 · United States
NHLBI NIH HHS · HL-58707 · United States
External Links
PubMed source DOI: 10.1016/s0092-8674(02)00754-7 PMC Full Text View journal details
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