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2014 Fiscal Year Final Research Report

Establishment of cell transplantation therapy for hepatic failure by hepatic stem/progenitor cells and/or hepatic organoids

Research Project

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Project/Area Number 24390304
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General surgery
Research InstitutionSapporo Medical University

Principal Investigator

MITAKA Toshihiro  札幌医科大学, 医学部, 教授 (50231618)

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)
Project Period (FY) 2012-04-01 – 2015-03-31
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
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.

Free Research Field

実験病理学

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Published: 2016-06-03  

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