Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand
Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand
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DOI：
10.1016/s0092-8674(02)00754-7
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发表时间：
2002-05-31
期刊：
影响因子：
64.5
通讯作者：
Rafii, S
中科院分区：
文献类型：
--
作者：
Heissig, B;Hattori, K;Rafii, S
骨髓 (BM) 内的干细胞处于静止状态，或者根据特定信号指示分化并动员至循环系统。在 BM 细胞中诱导的基质金属蛋白酶-9 (MMP-9) 会释放可溶性 Kit 配体 (sKitL)，从而使内皮细胞和造血干细胞 (HSC) 从静止状态转移到增殖状态。 BM 消融诱导 SDF-1，SDF-1 上调 MMP-9 表达，并导致 sKitL 脱落和 c-Kit(+) 干细胞/祖细胞的募集。在MMP-9(-/-)小鼠中，sKitL的释放和HSC运动受损，导致造血恢复失败并增加死亡率，而外源性sKitL在BM消融后恢复造血和存活。 MMP-9 释放 sKitL 使 BM 再生细胞能够转移到允许的血管生态位，有利于干/祖细胞池的分化和重建。
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.