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| Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand |
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| Author(s): Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MAS, Werb Z, Rafii S |
| Source: CELL Volume: 109 Issue: 5 Pages: 625-637 Published: MAY 31 2002 |
| Times Cited: 593 References: 35 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Rafii, S (reprint author), Cornell Univ, Coll Med, Dept Hematol Oncol, 1300 York Ave,Room D601, New York, NY 10021 USA |
Addresses:
1. Cornell Univ, Coll Med, Dept Hematol Oncol, New York, NY 10021 USA
2. Sloan Kettering Inst Canc Res, New York, NY 10021 USA
3. Cornell Univ, Coll Med, Div Med Genet, New York, NY 10021 USA
4. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 558GL |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |