Soluble c-kit receptor mobilizes hematopoietic stem cells to peripheral blood in mice
Soluble c-kit receptor mobilizes hematopoietic stem cells to peripheral blood in mice
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DOI：
10.1016/j.exphem.2004.01.004
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发表时间：
2004-04-01
影响因子：
2.6
通讯作者：
Murawaki, Y
中科院分区：
文献类型：
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作者：
Nakamura, Y;Tajima, F;Murawaki, Y
客观的。人们对于细胞因子将造血干细胞 (HSC) 从骨髓动员到外周血 (PB) 的机制知之甚少。一种假设是细胞因子破坏干细胞与骨髓基质的细胞粘附相互作用。 c-kit (s-kit) 的可溶部分结合干细胞因子 (SCF)，并能特异性阻断 SCF 结合 HSC 的能力。 材料和方法。为了检查 s-kit 的干细胞动员情况，我们从 s-kit 或粒细胞集落刺激因子 (G-CSF) 处理的小鼠中制备了 PB 单核细胞，并通过移植到经致死照射的 Ly-5.2 同系小鼠中来测定其集落形成能力和长期重建能力。结果。我们证实了已发表的研究结果，即人重组 s-kit 可以阻止 SCF 刺激的造血集落生长。然后我们发现 s-kit 可以将集落形成细胞从骨髓动员到 PB，并且我们在 s-kit 处理的小鼠的 PB 中发现了长期重建细胞。大多数 s-kit 动员的干细胞属于 CD34(+) 细胞群。我们还测试了G-CSF和s-kit之间的相加效应。移植G-CSF处理小鼠和G-CSF/s-kit处理小鼠的Lin(-)细胞的小鼠中供体细胞的平均百分比分别为44.6%和64.8%(p = 0.028)。结论。这些研究结果表明，具有长期植入能力的干细胞可以被s-kit动员，并且s-kit与G-CSF联合处理可显着提高植入效率，表明通过破坏c-kit和SCIF之间的动员来作为机制。 (C) 2004 年国际实验血液学学会。由爱思唯尔公司出版
Objective. The mechanisms of mobilization of hematopoietic stem cells (HSC) from bone marrow to peripheral blood (PB) by cytokines are poorly understood. One hypothesis is that cytokines disrupt cytoadhesive interactions of stem cells with bone marrow stroma. The soluble portion of c-kit (s-kit) binds stem cell factor (SCF) and can specifically block the ability of SCF to bind HSC.Materials and Methods. To examine stem cell mobilization by s-kit, we prepared PB mononuclear cells from s-kit- or granulocyte colony-stimulating factor (G-CSF)-treated mice and assayed their colony-forming abilities and their long-term reconstituting abilities by transplantation into lethally irradiated Ly-5.2 congenic mice.Results. We confirmed the published findings that human recombinant s-kit can block SCF-stimulated hematopoietic colony growing. We then found that s-kit could mobilize colony-forming cells from bone marrow to PB, and we found long-term reconstitution cells in the PB from s-kit-treated mice. The majority of s-kit-mobilized stem cells were in the CD34(+) cell population. We also tested the additive effect between G-CSF and s-kit. The mean percentages of donor cells in the mice transplanted with Lin(-) cells from the G-CSF-treated mice and the G-CSF/s-kit-treated mice were 44.6% and 64.8%, respectively (p = 0.028).Conclusions. These findings demonstrate that stem cells with long-term engraftment capabilities can be mobilized by s-kit, and that s-kit combined with G-CSF treatment leads to significant enhancement of engraftment efficiency, suggesting mobilization via disruption between c-kit and SCIF as the mechanism. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.