| Project/Area Number |
24390304
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TANIMIZU Naoki 札幌医科大学, 医学部, 准教授 (00333386)
ICHINOHE Norihisa 札幌医科大学, 医学部, 研究員 (80452978)
MIZUGUCHI Toru 札幌医科大学, 医学部, 准教授 (30347174)
HIRATA Koichi 札幌医科大学, 医学部, 教授 (50136959)
SUDO Ryo 慶應義塾大学, 理工学部, 准教授 (20407141)
KIKKAWA Yamato 東京薬科大学, 薬学部, 准教授 (20274227)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 肝幹・前駆細胞 / 細胞移植 / 胆管上皮細胞 / 分化 / 組織化 / 管腔形成 / IL17rb signal / Sox9 / 肝組織形成 / 再生医学 / Microvesicle / IL17RBシグナル / 分化転換 / 細胞外基質 / 組織形成 / マイクロＲＮＡ / 増殖因子 / 肝再生 / 肝幹細胞 / 肝前駆細胞 / 肝発生 / 類肝組織 / 共培養 |
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| Outline of Final Research Achievements |
We showed that a small part of Thy1-positive cells isolated from galactosamine-treated rat livers were hepatic stem/progenitors and could differentiate into hepatocytes by HGF/FGF via CD44-positive ones. However, it was hard for the progenitors to fully differentiate into mature hepatocytes. Transplantation of the Thy1-positive cells or rat bone marrow-derived mesenchymal cells stimulated the growth of resident hepatocytic progenitors in recipient rat livers by IL17B and IL25 that were secreted by sinusoidal endothelial and Kupffer cells, respectively. Laminin alpha 1 chains are necessary to form bile ducts in fetal mouse livers and expression of laminin alpha 5 chains is critical to differentiate into mature cholangiocytes. Plasticity of cholangiocytes to hepatocytes was rapidly lost after birth and Grhl2 expression is crucial to maturation of the cells.
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