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Development of a culture process for preventing transformation of normal hepatic stem cells and its application to regenerative medicine

防止正常肝干细胞转化的培养方法的开发及其在再生医学中的应用

基本信息

批准号：
17560693
负责人：
MATSUSHITA Taku
金额：
$ 2.24万
依托单位：
Sojo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

For regenerative medicine, it is necessary that stem cells will be proliferated in vitro to be attained a required cell number for the cell therapy. If normal stem cells transform in propagation process, these cells can not be applicable to regenerative medicine for the risk of tumor genesis. In fact, the stem cells and transformed tumor cells have similar characteristics and makers. In this research, we studied on development of new culture process for preventing transformation of human hepatic stem cells (hepatoblasts) using PIVKA-II (abnormal prothrombin) as a transformation maker, which is clinical tumor maker of hepatocytes.1, Effect of three dimensional culture on the transformation of hepatoblastsHuman hepatoblasts formed the three dimensional spheroid on the poly-L-glutamic acid coated dish. The PIVKA-II production rate of hepatoblasts was decreased and their transformation was prevented.2, Effect of hybrid liposomes on the induction of apoptosis of transformed hepatoblastsHybrid liposomes developed by Prof. Ueoka et al., are known to induce apoptosis of transformed tumor cells, but not of normal cells. In this study, It was suggested that decrease of PIVKA-II production and apoptosis induction of hepatoblasts by the treatment of hybrid liposomes.3, Effect of culture carriers on the transformation of hepatoblastsFor mass culture of human stem cells, it is necessary to study on material characteristics of culture carriers for preventing transformation of the cells. In this research, we examined several culture carriers. Macro porous carrier was better for cultivating human hepatoblasts at high density and preventing transformation of the cells.

对于再生医学，干细胞必须在体外增殖以达到细胞治疗所需的细胞数量。如果正常干细胞在增殖过程中发生转化，这些细胞就有发生肿瘤的风险，不能应用于再生医学。事实上，干细胞和转化的肿瘤细胞具有相似的特征和标志物。本研究以人肝细胞临床肿瘤标志物PIVKA-Ⅱ（异常凝血酶原）为转化标志物，探索了一种防止人肝干细胞（肝母细胞）转化的新培养方法。1、三维培养对肝母细胞转化的影响人肝母细胞在聚-L-谷氨酸包被的培养皿上形成三维球体。杂交脂质体对转化肝细胞凋亡的诱导作用Ueoka等开发的杂交脂质体，已知诱导转化的肿瘤细胞的凋亡，但不诱导正常细胞的凋亡。本研究表明，杂交脂质体处理肝母细胞可降低PIVKA-Ⅱ的产生，诱导细胞凋亡。3、培养载体对肝母细胞转化的影响对于人干细胞的大量培养，有必要研究防止细胞转化的培养载体的材料特性。在这项研究中，我们检查了几个文化载体。大孔载体有利于人成肝细胞的高密度培养和防止细胞转化。