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

Publication Type Academic Article
Authors Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett N, Crystal R, Besmer P, Lyden D, Moore M, Werb Z, Rafii S
Journal Cell
Volume 109
Issue 5
Pagination 625-37
Date Published 05/31/2002
ISSN 0092-8674
Keywords Bone Marrow, Cell Differentiation, Cell Movement, Hematopoietic Stem Cells, Matrix Metalloproteinase 9, Stem Cell Factor
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.
DOI 10.1016/s0092-8674(02)00754-7
PubMed ID 12062105
PubMed Central ID PMC2826110
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