Formation of steady-state oxygen gradients in vitro - Application to liver zonation
Formation of steady-state oxygen gradients in vitro - Application to liver zonation
复制标题
DOI：
10.1002/bit.10569
复制
发表时间：
2003-05-05
影响因子：
3.8
通讯作者：
Bhatia, SN
中科院分区：
文献类型：
--
作者：
Allen, JW;Bhatia, SN
我们已经开发了一种灌注生物反应器系统，其允许在细胞培养中形成稳态氧梯度。在这项研究中，在大鼠肝细胞培养物中形成梯度，以研究氧在调节细胞功能中的作用。在我们的平板反应器中的氧传输模型的开发，以估计在细胞表面的氧分布。实验测量的出口氧气浓度从各种流动条件下，用于验证模型的预测。我们表明，当出口处细胞表面的生理氧气梯度为76至5 mmHg O-2时，细胞活力可在24小时内维持。氧梯度与维持肝脏中的区域化代谢和解毒功能有关，称为区域化。在该系统中，反应器培养物中的生理氧梯度导致磷酸烯醇式丙酮酸羧激酶（主要位于上游）和细胞色素P450 213（主要位于下游）的异质分布，这与这些酶在体内的分布相关。氧梯度室提供了一种在连续范围的O-2张力上探测体外氧效应的方法。此外，该系统作为一个体外模型的分区，可以进一步扩展到研究梯度在缺血再灌注损伤，毒性和生物人工肝设计的作用。(C)2003 Wiley Periodicals，Inc.
We have developed a perfusion bioreactor system that allows the formation of steady state oxygen gradients in cell culture. In this study, gradients were formed in cultures of rat hepatocytes to study the role of oxygen in modulating cellular functions. A model of oxygen transport in our flat-plate reactor was developed to estimate oxygen distribution at the cell surface. Experimental measurements of outlet oxygen concentration from various flow conditions were used to validate model predictions. We showed that cell viability was maintained over a 24-h period when operating with a physiologic oxygen gradient at the cell surface from 76 to 5 mmHg O-2 at the outlet. Oxygen gradients have been implicated in the maintenance of regional compartmentalized metabolic and detoxification functions in the liver, termed zonation. In this system, physiologic oxygen gradients in reactor cultures contributed to a heterogeneous distribution of phosphoenolpyruvate carboxykinase (predominantly localized upstream) and cytochrome P450 213 (predominantly localized downstream) that correlates with the distribution of these enzymes in vivo. The oxygen gradient chamber provides a means of probing the oxygen effects in vitro over a continuous range of O-2 tensions. In addition, this system serves as an in vitro model of zonation that could be further extended to study the role of gradients in ischemia-reperfusion injury, toxicity, and bioartificial liver design. (C) 2003 Wiley Periodicals, Inc.