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首页> 外文期刊>Cytokine >Effect of hepatocyte growth factor on long term hematopoiesis of human progenitor cells in transgenic-sever combined immunodeficiency mice.
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Effect of hepatocyte growth factor on long term hematopoiesis of human progenitor cells in transgenic-sever combined immunodeficiency mice.

机译:肝细胞生长因子对转基因-重度联合免疫缺陷小鼠的人祖细胞长期造血的影响。

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摘要

Hepatocyte growth factor (HGF), which was originally isolated as a liver generating factor, enhances hematopoiesis. To study the effect of HGF on hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs), we generated severe combined immunodeficiency (SCID) mice producing human (h) HGF and/or stem cell factor (SCF) by transferring the relevant genes to fertilized eggs, and then transplanted hematopoietic progenitors from human cord blood into the transgenic (Tg) SCID mice. Six months after transplantation, a significantly larger number of human cells were found in the Tg SCID mice than in non-Tg controls. Characteristically, the recipient SCID mice producing h HGF (HGF-SCID) had a significantly increased number of h CD41+ cells, whereas the SCF-SCID recipients had more CD11b+ cells. Significantly large numbers of CD34+ progenitors were found in the SCID mice transferred with both h HGF and h SCF genes (HGF/SCF-SCID) when compared with HGF-SCID or SCF-SCID mice. These results imply that HGF supports the differentiation of progenitors in megakaryocyte lineage, whereas SCF supports that in myeloid lineage. The results also imply that HGF acts on HSCs/HPCs as a synergistic proliferative factor combined with SCF. We have demonstrated the advantage of the human cytokine-producing animal in the maintenance of human HSCs.
机译:最初被分离为肝生成因子的肝细胞生长因子(HGF)可增强造血功能。为了研究HGF对造血干细胞(HSC)和造血祖细胞(HPC)的作用,我们通过转移相关基因,产生了产生人(h)HGF和/或干细胞因子(SCF)的严重联合免疫缺陷(SCID)小鼠到受精卵,然后将人类脐带血的造血祖细胞移植到转基因(Tg)SCID小鼠中。移植六个月后,在Tg SCID小鼠中发现的人细胞数量明显多于非Tg对照。特征在于,产生h HGF(HGF-SCID)的受体SCID小鼠的h CD41 +细胞数量显着增加,而SCF-SCID受体的CD11b +细胞数量更多。与HGF-SCID或SCF-SCID小鼠相比,在同时携带h HGF和h SCF基因(HGF / SCF-SCID)的SCID小鼠中发现了大量CD34 +祖细胞。这些结果暗示,HGF支持巨核细胞谱系中祖细胞的分化,而SCF支持髓系谱系中祖细胞的分化。结果还暗示,HGF作为SCF的协同增生因子作用于HSC / HPC。我们已经证明了产生人类细胞因子的动物在维持人类HSC中的优势。

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