Establishment of the cell therapy for liver failure using hepatocytes derived from induced pluripotent stem cells

利用诱导多能干细胞来源的肝细胞建立治疗肝衰竭的细胞疗法

• 批准号: 23590977
• 负责人: YAMAMOTO Kazuhide
• 金额: $ 3.33万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590977/
• 关键词: iPS細胞; 肝細胞分化; 肝不全; 細胞移植; 再生医療; 肝細胞; 疾患モデル; 細胞治療

The purposes of this study are 1) to generate induced pluripotent stem (iPS) cells from the mouse tail, 2) to differentiate iPS cells to functional hepatocytes, and 3) to autograft differentiated cells into mice with liver failure. We isolated mouse fibroblast from mouse tail, transduced Oct3/4, Sox2, Klf4, c-Myc genes by using retroviral vectors established in Kyoto University, and generated mouse iPS cell lines. These mouse iPS cells were successfully differentiated into hepatocyte-like cells with supplementation of several growth factors and chemicals. We modified and improved the differentiation protocol and transplanted these cells into the portal vein of the immunodeficiency mouse, but teratomas were still formed. We conclude that further improvement of differentiation protocol for iPS cells is required to establish cell therapy for liver failure patients.

本研究的目的是：1)从小鼠尾部获得诱导多能干细胞（iPS）， 2)将诱导多能干细胞分化为功能性肝细胞，3)将分化的细胞自体移植到肝功能衰竭小鼠体内。我们从小鼠尾部分离成纤维细胞，利用京都大学逆转录病毒载体转导Oct3/4、Sox2、Klf4、c-Myc基因，制备小鼠iPS细胞系。这些小鼠iPS细胞在补充多种生长因子和化学物质的情况下成功分化为肝细胞样细胞。我们修改和完善了分化方案，并将这些细胞移植到免疫缺陷小鼠的门静脉，但仍形成畸胎瘤。我们认为，需要进一步完善iPS细胞的分化方案，以建立肝衰竭患者的细胞治疗。

项目成果

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Prospects for Creating Bioartificial Liver System with Induced Pluripotent Stem Cell Technology

利用诱导多能干细胞技术创建生物人工肝系统的前景

• DOI: 10.4172/2155-952x.1000157
• 发表时间: 2013
• 期刊: Journal of Biotechnology & Biomaterials
• 作者: Masaya Iwamuro;Hidenori Shiraha;Shuhei Nakaji;and Kazuhide Yamamoto
• 通讯作者: and Kazuhide Yamamoto

A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes.

• DOI: 10.1186/1475-925x-11-93
• 发表时间: 2012-12-07
• 期刊: Biomedical engineering online
• 影响因子: 3.9
• 作者: Iwamuro M;Shiraha H;Nakaji S;Furutani M;Kobayashi N;Takaki A;Yamamoto K
• 通讯作者: Yamamoto K