| Project/Area Number |
16390361
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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 |
General surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
IKAI Iwao Kyoto University Graduate School of Medicine, associate Professor, 医学研究科, 助教授 (60263084)
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| Co-Investigator(Kenkyū-buntansha) |
KOHNO Kenji Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Professor, 遺伝子教育研究センター, 教授 (50142005)
FUJII Hideaki Kyoto University Graduate School of Medicine, Instructor, 医学研究科, 助手 (50372587)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2004: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | Hepatic stem cells / ES cells / Cell transplantation therapy / TRECK mouse |
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| Research Abstract |
The aim of this research is establishment of new therapeutic modality for liver failure using hepatic stem cells. We have already reported as follows: 1) Enrichment of hepatic stem cells from mouse fetal and adult liver. 2) Thyl positive mesenchymal cells derived from mouse fetal liver promoted the in vitro maturation of hepatic stem cells into hepatocytes. Applying these findings, we have successfully produced hepatocytes differentiation from mouse embryonic stem cells. In this research, we applied "toxin receptor-mediated cell knockout (TRECK)" technique to produce alb-DTR transgenic mice, which expressed diphtheria toxin receptor (DTR) specifically on the surface of hepatocytes. We produced homozygous alb-DTR transgenic mice to induce dose-dependent and reproducible liver injury by diphtheria toxin administration. This is ideal model for investigation of functional remodeling of transplanted cells in the lethally injured liver similar to fulminant hepatitis. After the transplantatio
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n of 1×10^6 cells/body of hepatic stem/progenitor cells derived from E13.5 fetal liver of Green Fluorescent Protein (GFP)-transgenic mice into the liver of homozygous alb-DTR transgenic mice, we identified continuous growth and albumin production of transplanted cells in vivo. Furthermore, mortality of acute liver injury of transplanted group was statistically improved compared to that of non-transplanted group. In addition, we are now identifying the same results as improvement of mortality of alb-DTR mice by cell transplantation of hepatic stem/progenitor cells derived from mouse embryonic stem cells. On the other hand, morphologically identified two types of cells consisting of Thyl-positive mesenchymal cells derived from fetal liver were discriminated by the expression of glycoprotein 38 (gp38). Gp38-positive cells promoted in vitro maturation of hepatic stem/progenitor cells via cell-to-cell contact, wheras gp38-negative cells maintained undifferentiated state of hepatic stem/progenitor cells. We are now on the course of further investigation of gp38-positive and negative mesenchymal cells. Less
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