Establishment of cell transplantation therapy for hepatic failure by hepatic stem/progenitor cells and/or hepatic organoids
| 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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Report
(4 results)
Research Products
(121 results)
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[Journal Article] The impact of aging on morbidity and mortality after liver resection: a systematic review and meta-analysis2015
Author(s)
Mizuguchi T, Kawamoto M, Meguro M, Okita K, Ota S, Ishii M, Ueki T, Nishidate T, Kimura Y, Furuhata T, Hirata K
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Journal Title
Surgery Today
Volume: 45
Issue: 3
Pages: 259-270
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Soluble lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro2014
Author(s)
Kikkawa Y, Miwa T, Tanimizu N, Kadoya Y, Ogawa T, Katagiri F, Hozumi K, Nomizu M, Mizuguchi T, Hirata K, Mitaka T
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Journal Title
Experimental Cell Research
Volume: 328
Issue: 1
Pages: 197-206
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Wnt5a Signaling Mediates Biliary Differentiation of Fetal Hepatic Stem/Progenitor Cells2013
Author(s)
Kakinuma S, Kiyohashi K, Kamiya A, Sakamoto N, Nitta S, Yamanaka H, YoshinoK, Fujiki J, Murakawa M, Kusano-Kitazume A, Shimizu H, Okamoto R, Azuma S, Nakagawa M, Asahina Y, Tanimizu N, Kikuchi A, Nakauchi H, and *WatanabeM
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Journal Title
Hepatology
Volume: (in press)
Issue: 6
Pages: 2502-2513
DOI
Related Report
Peer Reviewed
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[Presentation] Clinical comparison of laparoscopic and open liver resection after propensity matching selection2015
Author(s)
Meguro M, Mizuguchi T, Kawamoto K, S. Ota, M. Ishii, Nishidate T, Okita K, Kimura Y, Hirata K
Organizer
10th Annual Academic Surgical Congress
Place of Presentation
Las Vegas, NV, USA
Year and Date
2015-02-03 – 2015-02-05
Related Report
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[Presentation] A novel technique of aqua-hanging maneuver method for large right liver tumors2014
Author(s)
Mizuguchi T, Hirata K, Meguo M, Ishii M, Okita K, Nishidate T, Ueki T, Ota S, Nobuoka T, Kimura Y, Kawamoto M
Organizer
The Scientific Meeting of the Japan-Hungary-Poland Surgical Society Triangle Sympoisium 2014
Place of Presentation
Keio University, Minato-ku, Tokyo
Year and Date
2014-10-17 – 2014-10-19
Related Report
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[Presentation] Soluble Lutheran glycoprotein/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro2014
Author(s)
Kikkawa Y, Miwa T, Tanimizu N, Kadoya Y, Ogawa T, Katagiri F, Hozumi K, Nomizu M, Mizuguchi T, Hirata K, Mitaka T
Organizer
American Society for Matrix Biology Biennial Meeting 2014
Place of Presentation
Marriott Key center, Cleveland, USA
Year and Date
2014-10-13
Related Report
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