A new selection system of suitable immunosuppressive drugs for each pancreatic islet transplantation using epigenetic analysis in a three-dimensional culture system

利用三维培养系统中的表观遗传学分析为每次胰岛移植建立合适的免疫抑制药物的新选择系统

• 批准号: 24659596
• 负责人: MASAKI NAGAYA
• 金额: $ 2.33万
• 依托单位: Meiji University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659596/
• 关键词: 糖尿病; 膵ランゲルハンス島; 膵島移植; 免疫抑制剤; ヒト糖尿病類似モデルブタ; エピゲノム; パーソナライズド

The problem with pancreatic islet transplantation for type 1 diabetes is that the immunosuppressive drugs used can damage pancreatic beta cells. This project aimed to establish a new selection system of suitable immunosuppressive drugs for each islet transplantation using epigenetic analysis in a three-dimensional culture system. We first isolated islets from a transgenic pig specifically expressing the green fluorescent protein in the beta cells. These islets were cultured in the presence of an immunosuppressive drug. Thereafter, epigenetic analysis of the islets was performed. With time, we observed epigenetic changes in the insulin gene promoter of the islets in a certain group, although there was no change in their configuration. Our system can evaluate the short-term influence of immunosuppressive drugs on pancreatic islets, the system may be used to determine which immunosuppressive drugs are specifically suitable for each human islet transplantation.

胰岛移植治疗1型糖尿病的问题是所用的免疫抑制药物会损害胰腺β细胞。本研究旨在建立一个新的选择系统，利用三维培养系统中的表观遗传学分析，为每个胰岛移植选择合适的免疫抑制剂。我们首先从β细胞中特异性表达绿色荧光蛋白的转基因猪中分离胰岛。这些胰岛在免疫抑制药物的存在下培养。此后，进行胰岛的表观遗传分析。随着时间的推移，我们观察到的表观遗传的变化，在胰岛素基因启动子的胰岛在一定的一组，虽然有没有改变，在他们的配置。本系统可以评价免疫抑制剂对胰岛的短期影响，可用于确定哪种免疫抑制剂特别适合于每种人胰岛移植。

项目成果

In vivo exogenic organ generation with organogenesis-disabled cloned pigs as a platform

以器官发生障碍的克隆猪为平台的体内外源器官生成

• 发表时间: 2014
• 作者: Matsunari H;Nakano K;Kanai T;Matsuda T;Maehara M;Watanabe M;Umeyama K;Nagaya M;Nakauchi H;Nagashima H
• 通讯作者: Nagashima H

Development of a feasible verification system for pluripotent stem cells using porcine parthenogenetic embryos

利用猪孤雌胚胎开发可行的多能干细胞验证系统

• 发表时间: 2012
• 作者: Nakano K;Watanabe M;Matsunari H;Matsuda T;Honda K;Maehara M;Kanai T;Arai Y;Umeyama K;Fu j i shiro S;Nagaya M;Nagashima H
• 通讯作者: Nagashima H

Transgenic pigs with pancreas-specific expression of green fluorescent protein.

• DOI: 10.1262/jrd.2014-006
• 发表时间: 2014
• 期刊: The Journal of reproduction and development
• 作者: Matsunari H;Kobayashi T;Watanabe M;Umeyama K;Nakano K;Kanai T;Matsuda T;Nagaya M;Hara M;Nakauchi H;Nagashima H
• 通讯作者: Nagashima H

In vivo generation of exogenic pancreas in apancreatic cloned pigs via blastocyst complementation

通过囊胚互补在无胰克隆猪体内产生外源胰腺

• 发表时间: 2013
• 作者: Matsunari H;Nakano K;Kanai T;Matsuda T;Maehara M;Watanabe M;Umeyama K;Nagaya M;Nakauchi H;Nagashima H
• 通讯作者: Nagashima H

In vitro modeling of al-antitrypsin deficiency using induced pluripotent stem cell-derived hepatocytes froma 1-antitrypsin deficient patients

使用 1-抗胰蛋白酶缺乏症患者的诱导多能干细胞来源的肝细胞进行 1-抗胰蛋白酶缺乏症的体外建模

• 发表时间: 2012
• 作者: Tafaleng EN;Han B;Hale P;Nagaya M;Duncan SA;Sto l s DB;Strom SC;Fox IJ
• 通讯作者: Fox IJ