QSB: Experimental and Computational Studies to Optimize Hepatocyte Function

Ierapetritou0424968这项研究的目标是开发基于系统的定量方法，考虑细胞新陈代谢的整体情况，包括多目标框架内的间隔室内过程。这是为了研究肝细胞的特性、特定功能在生物人工肝系统中的作用以及其性能的优化所必需的。他们的假设是，存在有限数量的对患者生存最关键的肝脏功能，有可能在肝细胞培养中显著上调这些功能，从而最大化细胞功能并减少生物人工肝所需的细胞质量。具体来说，这项研究的具体目的是：(1)表征和优化底物补充以增强肝细胞功能；(2)通过使用反义技术调节肝细胞功能，目标是检测不同的底物并验证特定目标1预测的不同途径的重要性；以及(3)开展定量分析，研究主要由于血浆浓度变化而引起的不确定性因素的影响。

Ierapetritou0424968The objective of this research is to develop systems-based quantitative approaches that consider the whole picture of cell metabolism, including intra and inter compartmental processes within a multi-objective framework. This is needed in order to investigate the characteristics of hepatocyte cells, the role of specific functions in bioartificial liver systems, and the optimization of their performance. Their hypothesis is that there is a finite number of hepatic functions which are most critical for patient survival, that it is possible to significantly upregulate these functions in hepatocyte cultures, and as a result, maximize cell function and reduce the cell mass required in the bioartificial liver. In particular, the specific aims for this research are: (1) to characterize and optimize substrate supplementation to enhance hepatocyte function, (2) to modulate the hepatocyte function through the use of antisense technology with the target to examine different substrates and validate the importance of different pathways as predicted by specific aim 1, and (3) to develop a quantitative analysis to study the effects of uncertainty considerations mainly due to variability of plasma concentration.