In‐depth physiological characterization of primary human hepatocytes in a 3D hollow‐fiber bioreactor
In‐depth physiological characterization of primary human hepatocytes in a 3D hollow‐fiber bioreactor
复制标题
3D 中空纤维生物反应器中原代人肝细胞的深入生理特征
DOI：
10.1002/term.418
复制
发表时间：
2011
影响因子：
3.3
通讯作者：
F. Noor
中科院分区：
文献类型：
--
作者：
Daniel Mueller;G. Tascher;U. Müller‐Vieira;D. Knobeloch;A. Nuessler;K. Zeilinger;E. Heinzle;F. Noor
随着主要研究重点转向三维（3D）培养技术，中空纤维生物反应器，允许形成组织样结构，显示出巨大的潜力，因为它们允许受控的体外培养，同时支持体内环境。在这项研究中，我们在连续运行> 2周的3D中空纤维生物反应器系统中对人肝细胞进行了系统和详细的生理学表征。原代人肝细胞在整个培养期间保持活力和功能。发现一般细胞功能（例如氧摄取、氨基酸代谢和底物消耗）和肝脏特异性功能（例如药物代谢能力和肝脏特异性代谢产物的产生）均稳定> 2周。正如预期，在肝脏特异性功能（即尿素和白蛋白生成）中观察到供体间变异性。此外，我们显示了在该设置中，原代人肝细胞在无血清条件下的维持。细胞分离后3周细胞色素P450的稳定基础活性证明了这种系统的药理学应用潜力。所提出的3D生物反应器系统中的肝细胞最终不仅可用于长期代谢和毒性研究，还可用于慢性重复给药毒性评估。版权所有© 2011约翰威利父子有限公司.
As the major research focus is shifting to three‐dimensional (3D) cultivation techniques, hollow‐fiber bioreactors, allowing the formation of tissue‐like structures, show immense potential as they permit controlled in vitro cultivation while supporting the in vivo environment. In this study we carried out a systematic and detailed physiological characterization of human liver cells in a 3D hollow‐fiber bioreactor system continuously run for > 2 weeks. Primary human hepatocytes were maintained viable and functional over the whole period of cultivation. Both general cellular functions, e.g. oxygen uptake, amino acid metabolism and substrate consumption, and liver‐specific functions, such as drug‐metabolizing capacities and the production of liver‐specific metabolites were found to be stable for > 2 weeks. As expected, donor‐to‐donor variability was observed in liver‐specific functions, namely urea and albumin production. Moreover, we show the maintenance of primary human hepatocytes in serum‐free conditions in this set‐up. The stable basal cytochrome P450 activity 3 weeks after isolation of the cells demonstrates the potential of such a system for pharmacological applications. Liver cells in the presented 3D bioreactor system could eventually be used not only for long‐term metabolic and toxicity studies but also for chronic repeated dose toxicity assessment. Copyright © 2011 John Wiley & Sons, Ltd.
登录
查看更多内容
影响因子：
6.1
作者：
Domansky K;Inman W;Serdy J;Dash A;Lim MH;Griffith LG
通讯作者：
Griffith LG
影响因子：
2.1
作者：
Ulker, Pinar;Meiselman, Herbert J.;Baskurt, Oguz K.
通讯作者：
Baskurt, Oguz K.
影响因子：
3
作者：
Gerlach, Joerg C.;Hout, Mariah;Zeilinger, Katrin
通讯作者：
Zeilinger, Katrin
影响因子：
1.9
作者：
DEMETRIOU, AA;ROZGA, J;MAKOWKA, L
通讯作者：
MAKOWKA, L