Inventory of Artificial Liver Support based on the mixed culture system of Hepatocytes with Ito cells

基于肝细胞与伊藤细胞混合培养体系的人工肝支持盘点

基本信息

批准号：
11308036
负责人：
ISHII Hiromasa
金额：
$ 22.66万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Cell- cell interactions are important in embryogenesis, in adult physiology and pathophysiology of many disease processes. Co-cultivation of parenchymal and mesenchymal cells has been widely utilized as a paradigm for the study of cell-cell interactions in vitro. In addition, co-cultures of two cell types provide highly functional tissue constructs for use in therapeutic or investigational applications. In this study, we utilize micro fabrication techniques to localize both cell populations in patterned configulations on rigid substrates. We were able to control the level of homotypic interaction in cultures of single cell type and the degree of heterotypic contact in co-culture over a wide range. We have experimentally shown that stellate cells numbers and increased heterotipic cell-cell interactions influences hepatocellular functions. Organs are composed of many individual cell types and together responsible for orchestrating tissue functions. We could mimic liver function in vitro … More and utilize this sytem to elucidate fundamental factors of liver development. We monitored liver -specific functions by urea synthesis and albumin secretion, varied 2-fold with increasing heterotipic cell-cell interactions. Urea is a marker of metabolic function and albumin secretion is a marker of synthetic function. We also investigated lipid metabolism and P450 enzymatic detoxification activity. All data indicated that increasing heterotipic cell-cell interactions contributed maintaining liver specific functions. Moreover we could induced some hepatocyte specific protein expression in ES cells when we co-cultivate ES cells in this system. These evidence indicate that this approach will allow further elucidation of the complex interplay betweentwo cell types as they form a functional model tissue in vitro or as they interact in vivo to form functional organ. Although further investigations are necessary to develop artificial liver for clinical use, this study has clearly shown that appropriate co-clutivation method is numers of advantage over the other approaches. Less

细胞 - 细胞相互作用在胚胎生成中很重要，并且在体外，在体外，间充质细胞已被广泛用作螺柱 - 细胞相互作用的范式。 Ize微型制造技术将两个细胞在刚性底物上普及在单一类型的培养物中在体外的组织功能……更多，并利用该系统来阐明肝脏因子的肝脏特异性功能，而白蛋白分泌尿素是代谢功能的标志在ES细胞中诱导了一些肝细胞特异性蛋白，我们在这些系统中共同培养ES细胞。有机体。