Sugiura Kikuya, Taketani Shigeru, Yoshimura Tomoo, Nishino Tomoyoshi, Nishino Naoki, Fujisawa Jun-ichi, Hisha Hiroko, Inaba Toshio, Ikehara Susumu
Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai City, Osaka, Japan.
Cytokine. 2007 Mar;37(3):218-26. doi: 10.1016/j.cyto.2007.04.001. Epub 2007 May 23.
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.
肝细胞生长因子（HGF）最初作为一种肝脏生成因子被分离出来，它能增强造血功能。为了研究HGF对造血干细胞（HSCs）和造血祖细胞（HPCs）的影响，我们通过将相关基因导入受精卵，培育出了能产生人（h）HGF和/或干细胞因子（SCF）的严重联合免疫缺陷（SCID）小鼠，然后将人脐带血中的造血祖细胞移植到转基因（Tg）SCID小鼠体内。移植6个月后，在Tg SCID小鼠中发现的人细胞数量明显多于非Tg对照小鼠。其特点是，产生h HGF的受体SCID小鼠（HGF-SCID）中h CD41+细胞数量显著增加，而SCF-SCID受体小鼠中CD11b+细胞更多。与HGF-SCID或SCF-SCID小鼠相比，在同时导入h HGF和h SCF基因的SCID小鼠（HGF/SCF-SCID）中发现了大量的CD34+祖细胞。这些结果表明，HGF支持祖细胞向巨核细胞系分化，而SCF支持其向髓系分化。结果还表明，HGF作为一种与SCF联合的协同增殖因子作用于HSCs/HPCs。我们已经证明了产生人细胞因子的动物在维持人HSCs方面的优势。
