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

被引:1504
作者
Heissig, B
Hattori, K
Dias, S
Friedrich, M
Ferris, B
Hackett, NR
Crystal, RG
Besmer, P
Lyden, D
Moore, MAS
Werb, Z
Rafii, S
机构
[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
关键词
D O I
10.1016/S0092-8674(02)00754-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:625 / 637
页数:13
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