QSB: Experimental and Computational Studies to Optimize Hepatocyte Function

Ierapetritou0424968本研究的目的是开发基于系统的定量方法，该方法考虑细胞代谢的整体情况，包括多目标框架内的房室内和房室间过程。这是为了研究肝细胞的特性，生物人工肝系统中特定功能的作用，以及其性能的优化所需要的。 他们的假设是，有有限数量的肝功能对患者的生存至关重要，有可能在肝细胞培养物中显著上调这些功能，从而最大限度地提高细胞功能并减少生物人工肝所需的细胞量。这项研究的具体目标是：（1）表征和优化底物补充以增强肝细胞功能，（2）通过使用靶向反义技术来调节肝细胞功能，以检查不同底物并验证特定目的1所预测的不同途径的重要性，和（3）开发定量分析，以研究主要由于血浆浓度的变异性引起的不确定性考虑的影响。

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.