| Project/Area Number |
12470256
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
HIROSE Tetsuro Institute for Frontier Medical Sciences, Instructor, 再生医科学研究所, 助手 (00314279)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATSUJI Norio Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (80237312)
YAMAOKA Yoshio Graduate School of Medicine., Professor, 医学研究科, 教授 (90089102)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥10,900,000 (Direct Cost: ¥10,900,000)
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| Keywords | Embryonic Stem Cells / Hepatic Progenitor Cells / Endoderm / Transgenic Mice / Hepatocyte Growth Factor / Bone Marrow Cells / 肝細胞 / 分化誘導 / 蛍光励起セルソーター / 内胚葉レポーティングES細胞 / Cre / loxP / アルブミン / HGF |
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| Research Abstract |
We have established a detection system for hepatocytes induced from embryonic stem cells using a reporter gene construct that includes Green Fluorescent Protein (GFP) regulated under the enhancer/ promoter of the albumin gene, one of the endodermal markers present during the course of development. We have modified the reporter gene construct using the insulator sequence and the Cre-/loxP system because the albumin enhancer/promoter has weak activity, and the expression of albumin gene is affected by the promoter of the drug resistant gene included in the construct. Furthermore, we are now going to verify the efficacy of this system through the investigation of transgenic mice which have been produced with this reporter gene construct. In addition, we intend to use immature and mature hepatocytes induced from embryonic *m cells for cell therapy treatment of liver diseases. For this purpose, we have also investigated the role of growth factors and hepatic progenitor/stem cells on liver r
… More
egeneration. Consequently, we discovered that hepatocyte growth factor (HGF) attenuates the hepatic ischemia-reperfusion injury due to the reduction of oxidative stress (Oe et al., J. Hepatology 2001). Furthermore, we determined that bone marrow cells differentiate into vascular endothelial cells and Kupper cells in the regenerative liver after partial hepatectomy, while not into hepatocytes as previously reported in the animal model of fluminant hepatitis (Fujii et al., J. Hepatology 2002). We also established an effective isolation method and a highly efficient gene transfer system for mouse fetal hepatic progenitor cells (Yasuchika et al., Hepatology 2002). We intend to investigate the characteristics of hepatic progenitor/stem cells and establish a maturation system for these cells using the reporter gene construct as previously described. We can isolate hepatic progenitor cells from adult liver tissue using the same method as from fetal liver tissue (Azuma et al., Hepatology 2003), and are now going to investigate the characteristics of these cells. Less
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