The establishment of induction method from iPs cells to hepatocyte:For cell transplantation

iPs细胞向肝细胞诱导方法的建立：用于细胞移植

• 批准号: 22791275
• 负责人: ISHII Takamichi
• 金额: $ 2.58万
• 依托单位: Kyoto 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 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791275/
• 关键词: 肝臓外科学; iPS 細胞; 細胞移植治療; 肝幹細胞; iPS細胞

Recently, orthotopic liver transplantation is unique and the most efficient treatment for end-stage liver disease. But, the therapy has the issues of donor shortage and immune rejection. Then, a hepatocyte transplantation is listed as a alternative therapy for liver transplantation, we investigated hepatocyte transplantation.First, we selected iPS cells and mesenchymal stem cells as a cell source, and we tried and succeeded to induce differentiation of human induced pluripotent stem cells and human mesenchymal stem cells to hepatocyte like cells in vitro.In particular, the cells which was provided with extra cellular matrix and cytokines, expressed albumin and other hepatocyte marker in RT -PCR and immunohistochemistry. We transplanted these hepatocyte like cells into livers of SCID rats. In rats which were transplanted hepatocyte like cells derived from mesenchymal stem cells, we detected the albumin positive cells in the liver, in some of those rats, the serum level of human albumin increased.And then, in rats which were transplanted hepatocyte like cells derived from iPS cells, the albumin positive cells were detected in the liver .This result indicated that we can use iPS cells and mesenchymal stem cells as a cell source of hepatocyte transplantation.

目前，原位肝移植是治疗终末期肝病最有效的方法。但是，这种疗法存在供体短缺和免疫排斥的问题。随后，肝细胞移植被列为肝移植的一种替代疗法，我们对肝细胞移植进行了研究。首先，我们选择iPS细胞和间充质干细胞作为细胞来源，尝试并成功地在体外诱导人多能干细胞和人间充质干细胞向肝细胞样细胞分化。特别是在RT -PCR和免疫组织化学中，提供细胞外基质和细胞因子的细胞表达白蛋白等肝细胞标志物。我们将这些肝细胞样细胞移植到SCID大鼠肝脏中。在移植间充质干细胞类肝细胞的大鼠中，我们在肝脏中检测到白蛋白阳性细胞，其中一些大鼠的血清白蛋白水平升高。然后，在移植肝细胞的大鼠中，从iPS细胞中提取的肝细胞，在肝脏中检测到白蛋白阳性细胞。这一结果表明，我们可以利用iPS细胞和间充质干细胞作为肝细胞移植的细胞来源。

项目成果

Alfa-fetoprotein producing cells act as cancer progenitor cells in human cholangiocellular carcinoma.

产生甲胎蛋白的细胞在人胆管细胞癌中充当癌症祖细胞。

• 发表时间: 2010
• 期刊: Cancer Letters
• 影响因子: 9.7
• 作者: Takamichi Ishii;et al.
• 通讯作者: et al.

Differentiation of Human Embryonic Stem Cell into Functional Hepatocyte-like Cells, Stem Cells and Cancer Stem Cells, Volume 2

人胚胎干细胞分化为功能性肝细胞样细胞、干细胞和癌症干细胞，第 2 卷

• 发表时间: 2012
• 作者: Ishii T;Yasuchika K;Ikai I.;Takamichi Ishii
• 通讯作者: Takamichi Ishii

大量肝切除後の急性肝不全に対する肝細胞自家移植を用いた治療戦略

自体肝细胞移植治疗大面积肝切除术后急性肝衰竭的治疗策略

• 发表时间: 2012
• 作者: 上村 良;石井 隆道;佐々木 直也;梶原 正俊;福光 剣,斉藤 美知子,河野 憲二,猪飼伊和夫,安近 健太郎,上本 伸二;喜多貞彦ほか
• 通讯作者: 喜多貞彦ほか

A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers.

• DOI: 10.1007/s11626-010-9354-7
• 发表时间: 2011-01
• 期刊: IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
• 影响因子: 2.1
• 作者: Konishi, Sayuri;Yasuchika, Kentaro;Ishii, Takamichi;Fukumitsu, Ken;Kamo, Naoko;Fujita, Naoya;Ikai, Iwao;Uemoto, Shinji
• 通讯作者: Uemoto, Shinji

Differentiation of Hunan Embryonic Stem Cell into Functional Hepatocyte-like Cells

湖南胚胎干细胞向功能性肝细胞样细胞的分化

• 发表时间: 2012
• 作者: Ishii T;Yasuchika K;Ikai I.;Takamichi Ishii;Takamichi Ishii and;Takamichi Ishii
• 通讯作者: Takamichi Ishii