Studies of regenerative medicine on differentiation into hepatic and bile duct cells for preclinical trial to surgery
| Project/Area Number |
18390343
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
TERAOKA Hirobumi (2007) Tokyo Medical and Dental University, Medical Research Institute, Professor (30019137)
寺本 研一 (2006) 東京医科歯科大学, 大学院医歯学総合研究科, 助教授 (80197813)
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| Co-Investigator(Kenkyū-buntansha) |
ARII Shigeki Tokyo Medical and Dental University, Graduate School of Medicine, Professor (50151171)
TANAKA Yujiro Tokyo Medical and Dental University, Graduate School of Medicine, Professor (70236644)
ISEKI Sachiko Tokyo Medical and Dental University, Graduate School of dentistry, Assistant Professor (80251544)
YOSHIOKA Kenichi Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor (70321916)
TAKASE Kozo Tokyo Medical and Dental University, Graduate School of Medicine, Professor (90211333)
斉藤 佳子 東京医科歯科大学, 難治疾患研究所, 教務職員 (50178969)
朝比奈 欣治 東京医科歯科大学, 難治疾患研究所, 助手 (40345294)
寺岡 弘文 東京医科歯科大学, 難治疾患研究所, 教授 (30019137)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,390,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2007: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2006: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | ES cell / Hepatocyte / Regenerative medicine / Cell transplantation / Bile duct / Hepatoblast / ex utero surgery / iPS cell / 肝機能障害治療 / 肝外胆管 |
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| Research Abstract |
Although the intrahepatic bile duct has been suggested to be a source of hepatic progenitor cells in the severely damaged liver, little attention has been paid to the question of whether hepatic progenitor cells exist in the extrahepatic bile duct (EHBD). We examined the phenotypic changes of the mouse EHBD following the bile duct ligation. After bile duct ligation, the number of c-kit-positive epithelilal cells increased in the EHBD. The ligated EHBD expressed mRNA for hepatic progenitor cell markers. Hepatocyte markers were also transiently detected in the EHBD and gall bladder after a bile duct ligation. Hepatic progenitor cells positive for both c-kit and albumin were found in the cultured EHBD population. These results suggest a potential of the EHBD and gall bladder as useful transplantable sources for liver injury.
Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepati
… More
c developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or α-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells became mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse ES cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.
We revealed involvement of VEGF in efficient differentiation into hepatocyte-like cells, biological function of the undifferentiated cell marker gene DPPA4, and epigenetic regulation of the mature hepatocyte marker gene MAT1A. Less
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] Human cord blood cells transplanted into chronic-damaged liver exhibit similar characteristics to functional hepatocytes.2007
Author(s)
Kakinuma S, Asahina K, Okamura K, Teramoto K, Tateno C, Yoshizato K, Tanaka Y, Yasumizu T, Sakamoto N, Watanabe M, Teraoka H
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Journal Title
Transplantation Proceedings 39
Pages: 240-243
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Hepatocyte differentiation and eratoma formation after transplantation of embryoid body cells derived from murine and primate embryonic stem cells into injured mouse liver2006
Author(s)
Teramoto K, Asahina K, Okamura K, Kumashiro Y, Me T, Shimizu-Saito K, Teraoka H, Arii S
Organizer
World Transplant Congress, Hynes Convention Center
Place of Presentation
Boston, MA, USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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