Analysis on molecular mechanisms of proliferation and differentiation of hepatic stem/progenitor cells and development of animal model for treatment of liver diseases using hepatic stem cells

肝干/祖细胞增殖分化的分子机制分析及肝干细胞治疗肝病动物模型的建立

• 批准号: 22790632
• 负责人: KAKINUMA Sei
• 金额: $ 2.5万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790632/
• 关键词: 肝臓学; 再生医学; 移植; 細胞・組織; 発生・分化; 肝疾患治療; 肝細胞移植

Investigators of this research project have analyzed on the molecular mechanisms of differentiation and proliferation of primary hepatic stem/progenitor cells purified by cell surface markers. We have also studied whether modulation of several molecules improves therapeutic efficacy of transplantation using hepatic stem/progenitor cells. We found that Wnt5a and Wnt5a-related molecules control the biliary differentiation of hepatic stem/progenitor cells. Next, our data indicated that loss of MMP2 or MMP14 worsens the efficacy of transplantation using hepatic stem/progenitor cells. These studies contribute to the progress of regenerative medical science and autologous stem cell therapy against liver diseases.

本课题研究人员通过细胞表面标记物纯化原代肝干/祖细胞，分析其分化增殖的分子机制。我们还研究了几种分子的调节是否提高了使用肝干/祖细胞的移植的治疗效果。我们发现Wnt 5a和Wnt 5a相关分子控制肝干/祖细胞的胆管分化。接下来，我们的数据表明，MMP 2或MMP 14的缺失会影响使用肝干/祖细胞的移植的功效。这些研究有助于再生医学科学和自体干细胞治疗肝病的进展。

项目成果

Therapeutic model of hepatic cell transplantation without genetic liver injury in recipients

受者无遗传性肝损伤的肝细胞移植治疗模型

• 发表时间: 2010
• 作者: Kakinuma S;Kamiya A;Sakamoto N;Watanabe M;Nakauchi H.
• 通讯作者: Nakauchi H.

Noncanonical Wnt経路による肝幹/前駆細胞の分化制御

非经典 Wnt 通路调控肝干/祖细胞分化

• 发表时间: 2011
• 作者: 幾世橋佳;柿沼晴;渡辺守
• 通讯作者: 渡辺守

MMP-2 and MMP-14 derived from donor cells enhance therapeutic efficacy of liver cell transplantation in mice

供体细胞来源的 MMP-2 和 MMP-14 增强小鼠肝细胞移植的治疗效果

• 发表时间: 2011
• 作者: Kakinuma S;Sakamoto N;Watanabe M;et al.
• 通讯作者: et al.

IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones.

• DOI: 10.1016/j.virol.2010.07.041
• 发表时间: 2010-11
• 期刊: Virology
• 影响因子: 3.7
• 作者: G. Suda;N. Sakamoto;Yasuhiro Itsui;M. Nakagawa;Megumi Tasaka-Fujita;Yusuke Funaoka;Takako Watanabe;S. Nitta;Kei Kiyohashi;Seishin Azuma;S. Kakinuma;K. Tsuchiya;M. Imamura;N. Hiraga;K. Chayama;Mamoru Watanabe

Conference Study Group. Serum interleukin-6 levels can predict resistance to treatment of chronic hepatitis C infection with pegylated-interferon alpha 2b plus ribavirin

会议研究组。

• 发表时间: 2011
• 期刊: Antivir Ther
• 影响因子: 1.2
• 作者: Ueyama M;Nakagawa M;Sakamoto N;Onozuka I;Funaoka Y;Watanabe T;Nitta S;Kiyohashi K;Kitazume A;Murakawa M;Nishimura-Sakurai Y;Sekine-Osajima Y;Itsui Y;Azuma S;Kakinuma S;Watanabe M and the Ochanomizu-Liver
• 通讯作者: Watanabe M and the Ochanomizu-Liver