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Enhanced oxygen availability improves liver-specific functions of the AMC bioartificial liver.

机译:增强的氧气利用率改善了AMC生物人工肝的肝脏特异性功能。

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Long-term culturing of primary porcine hepatocytes (PPH) inside the Academic Medical Center (AMC)-bioartificial liver is characterized by increased anaerobic glycolysis. Recommendations to increase oxygen availability were proposed in a previous numerical study and were experimentally evaluated in this study. Original bioreactors as well as new configuration bioreactors with 2.2-fold thinner nonwoven matrix and 2-fold more capillaries were loaded with PPHs and oxygenated with different gas oxygen pressures resulting in medium pO(2) (pO(2-med)) of either 135-150 mm Hg or 235-250 mm Hg. After 6 days culturing, new configuration bioreactors with pO(2-med )of 250 mm Hg showed significantly reduced anaerobic glycolysis, 60% higher liver-specific functions, and increased transcript levels of five liver-specific genes compared to the standard bioreactor cultures. Changed bioreactor configuration and increasing pO(2-med) contributed equally to these improvements. Histological examination demonstrated small differences in cell organization. In conclusion, higher metabolic stability and liver-specific functionality was achieved by enhanced oxygen availability based on a prior modeling concept.
机译:在学术医学中心(AMC)-生物人工肝内长期培养原代猪肝细胞(PPH)的特点是厌氧糖酵解增加。在先前的数值研究中提出了增加氧气利用率的建议,并在此研究中进行了实验评估。原始生物反应器以及新配置的生物反应器(具有2.2倍较薄的非织造基质和2倍多的毛细管)装载有PPH,并用不同的气体氧气压力充氧,从而产生135的中等pO(2)(pO(2-med)) -150毫米汞柱或235-250毫米汞柱。培养6天后,与标准生物反应器培养物相比,具有250 mm Hg pO(2-med)的新配置生物反应器显示出明显减少的厌氧糖酵解,60%更高的肝特异性功能以及五个肝特异性基因的转录水平增加。改变的生物反应器配置和增加的pO(2-med)同样对这些改进做出了贡献。组织学检查显示细胞组织的微小差异。总之,基于先前的建模概念,通过提高氧气的利用率,可以获得更高的代谢稳定性和肝脏特异性功能。

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