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MEMS platform for study of dynamic cell-cell interaction

用于研究动态细胞间相互作用的 MEMS 平台

基本信息

批准号：
7106853
负责人：
Elliot E Hui
金额：
$ 4.83万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-01 至 2006-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7106853
关键词：
biological signal transduction biomechanics cadherins cell cell interaction cell differentiation gene expression immunofluorescence technique liver cells liver disorder postdoctoral investigator silicon

项目摘要

DESCRIPTION (provided by applicant): Progress in cell-based therapies for liver disease currently remains slow and highly empirical due to the fact that the key determinants of liver-specific function in isolated hepatocytes remain unknown. Heterotypic (hepatocyte/non-parenchymal) cell-cell contact has been shown to induce differentiated function in hepatocytes both in embryogenesis and in vitro. However, neither the molecular mechanism by which cell-cell interactions impact differentiation nor the dynamics of this response have been elucidated, in part, due to the limitations of current experimental techniques. The recent development of MEMS (microelectromechanical systems) technology has enabled the creation of complex mechanical devices with microscopic dimensions through the use of integrated circuit microfabrication methods. Taking advantage of this technology, the proposed research intends to study the dynamics of hepatocyte response to cell-cell contact with non-parenchymal cells using a microfabricated platform that enables the user to initiate and disrupt heterotypic contact at various time points of interest. The specific questions addressed will be the correlation between the formation of heterotypic adherents junctions and the onset of liver-specific gene expression, the necessity of continuous signaling to maintain differentiated functions, and the role of reciprocal signaling on the inductive capability of non-parenchymal cells. Better understanding of the mechanisms and dynamics of hepatocyte differentiation has important implications in liver development and hepatic tissue engineering. In addition, this platform will also find broad utility in the study of cell-cell interactions in many different organ systems.

描述（由申请人提供）：由于分离的肝细胞中肝脏特异性功能的关键决定因素仍然未知，目前肝病的细胞疗法进展缓慢且高度经验性。异型（肝细胞/非实质）细胞-细胞接触已被证明在胚胎发生和体外诱导肝细胞的分化功能。然而，细胞-细胞相互作用影响分化的分子机制和这种反应的动力学都没有得到阐明，部分原因是目前实验技术的局限性。MEMS（微机电系统）技术的最新发展使得能够通过使用集成电路微制造方法来创建具有微观尺寸的复杂机械装置。利用这项技术，拟议的研究旨在研究肝细胞对细胞与非实质细胞接触的反应动力学，使用微制造平台，使用户能够在感兴趣的各个时间点启动和破坏异型接触。解决的具体问题将是异型粘附连接的形成和肝特异性基因表达的发病之间的相关性，连续的信号传导的必要性，以维持分化的功能，以及相互信号传导对非实质细胞的诱导能力的作用。深入了解肝细胞分化的机制和动力学对肝发育和肝组织工程具有重要意义。此外，该平台还将在许多不同器官系统中的细胞-细胞相互作用的研究中发现广泛的实用性。