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首页> 外文期刊>Journal of Cellular Physiology >Three dimensional cultures of rat liver cells using a natural self-assembling nanoscaffold in a clinically relevant bioreactor for bioartificial liver construction.
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Three dimensional cultures of rat liver cells using a natural self-assembling nanoscaffold in a clinically relevant bioreactor for bioartificial liver construction.

机译：三维培养的大鼠肝细胞使用自然自我组装的nanoscaffold临床相关的人工生物反应器肝脏建设。

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Till date, no bioartificial liver (BAL) procedure has obtained FDA approval or widespread clinical acceptance, mainly because of multifactorial limitations such as the use of microscale or undefined biomaterials, indirect and lower oxygenation levels in liver cells, short-term undesirable functions, and a lack of 3D interaction of growth factor/cytokine signaling in liver cells. To overcome preclinical limitations, primary rat liver cells were cultured on a naturally self-assembling peptide nanoscaffold (SAPN) in a clinically relevant bioreactor for up to 35 days, under 3D interaction with suitable growth factors and cytokine signaling agents, alone or combination (e.g., Group I: EPO, Group II: Activin A, Group III: IL-6, Group IV: BMP-4, Group V: BMP4 + EPO, Group VI: EPO + IL-6, Group VII: BMP4 + IL-6, Group VIII: Activin A + EPO, Group IX: IL-6 + Activin A, Group X: Activin A + BMP4, Group XI: EPO + Activin A + BMP-4 + IL-6 + HGF, and Group XII: Control). Major liver specific functions such as albumin secretion, urea metabolism, ammonia detoxification, phase contrast microscopy, immunofluorescence of liver specific markers (Albumin and CYP3A1), mitochondrial status, glutamic oxaloacetic transaminase (GOT) activity, glutamic pyruvic transaminase (GPT) activity, and cell membrane stability by the lactate dehydrogenase (LDH) test were also examined and compared with the control over time. In addition, we examined the drug biotransformation potential of a diazepam drug in a two-compartment model (cell matrix phase and supernatant), which is clinically important. This present study demonstrates an optimized 3D signaling/scaffolding in a preclinical BAL model, as well as preclinical drug screening for better drug development.
机译：至今为止,没有生物人工肝(BAL)过程已获得FDA批准或广泛的临床吗接受,主要是因为多因素疾病如使用微尺度或限制未定义的生物材料,间接和较低肝细胞的氧化水平,短期的不受欢迎的功能,和缺乏3 d相互作用的生长因子/细胞因子信号在肝细胞。限制,主要鼠肝细胞培养自然自组装肽在临床相关nanoscaffold (SAPN)生物反应器35天,在3 d与合适的生长因子和交互细胞因子信号代理,单独或组合(例如,组我:EPO(促红细胞生成素)组II:激活素A组三世:il - 6,第四组:BMP-4集团V: BMP4 + EPO(促红细胞生成素)六:组主任+ IL-6集团,集团七:BMP4 + IL-6,Group A +八:Activin EPO Group九:IL-6 +,第十二:控制)。如白蛋白分泌,尿素代谢,氨解毒、相衬免疫荧光显微镜,肝脏特定标记(白蛋白和CYP3A1),线粒体地位,谷氨酸草酰乙酸的转氨酶(了)活动中,谷氨酸丙酮转氨酶(GPT)活动,细胞膜的稳定性乳酸脱氢酶(LDH)测试也检查并与控制时间。此外,我们研究了药物潜在的安定药物生物转化两舱制模型(阶段和细胞矩阵上层清液)是临床上重要的。本研究展示了一个优化3 d信号/支架在临床前BAL模型中,以及临床前药物筛选更好药物开发。

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