Treamtent of liver cirrhosis using inoculation of proliferative hepatocyte and gene transduction of antisense for mRNA of collagenase inhibitor.

利用增殖肝细胞接种和胶原酶抑制剂mRNA反义基因转导治疗肝硬化。

• 批准号: 08457293
• 负责人: TAGUCHI Yoshio
• 金额: $ 4.54万
• 依托单位: TOHOKU University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457293/
• 关键词: gene therapy; liver cirrhosis; antisense; hybridoma; 遺伝子導入; アンチ・センス

Experiment 1 : For establishment of a animal model with liver cirrhosis, CCl_4 and dimethyl nitrosoamine (DMNA) were administered to mouse and rat. Liver of animals with administration of CCl_4 were cirrhotic but parenchymal hepatocyte was injured so severely.Experiment 2 : For making hybridoma which has function of hepatocyte and proliferates, we tried to make cell fusion equipment using laser. Using this device, we could make hybridoma from mouse myeloma cells and lymphocytes.Experiment 3 : For treatment of cell function by gene transduction, we carried out the preliminary study that antisense for mRNA of TNF was encapsuled with HVJ liposome and was transfected to Kupffer cells. With antisense therapy, production of TNF decreased to 40%.

实验1：为建立肝硬化动物模型，给小鼠和大鼠施用CCl_4和二甲基亚硝胺(DMNA)。给予CCl_4的动物肝脏发生肝硬化，但实质肝细胞损伤严重。实验二：为了制作具有肝细胞功能并能增殖的杂交瘤，我们尝试利用激光制作细胞融合设备。利用该装置，我们可以制备小鼠骨髓瘤细胞和淋巴细胞的杂交瘤。 实验3：为了通过基因转导治疗细胞功能，我们进行了将TNF mRNA的反义分子用HVJ脂质体包裹并转染到Kupffer细胞的初步研究。通过反义疗法，TNF 的产生减少至 40%。