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.
authors.affiliation: Division of Hematology-Oncology, Cornell University Medical College, New York, NY 10021, USA.
authors.forename: Beate
authors.initials: B
authors.lastname: Heissig
authors.forename: Koichi
authors.initials: K
authors.lastname: Hattori
authors.forename: Sergio
authors.initials: S
authors.lastname: Dias
authors.forename: Matthias
authors.initials: M
authors.lastname: Friedrich
authors.forename: Barbara
authors.initials: B
authors.lastname: Ferris
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.forename: Peter
authors.initials: P
authors.lastname: Besmer
authors.forename: David
authors.initials: D
authors.lastname: Lyden
authors.forename: Malcolm A S
authors.initials: MA
authors.lastname: Moore
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology*; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency* / Q000235:genetics; D008533:Megakaryocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology; D019089:Stem Cell Factor / Q000378:metabolism* / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016228:Endothelial Growth Factors; D007166:Immunosuppressive Agents; D008222:Lymphokines; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020780:Matrix Metalloproteinase 9; D005472:Fluorouracil