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模块化生物反应器中脂肪组织、内皮细胞和肝细胞培养物的流量调节葡萄糖和脂质代谢。

Flow-regulated glucose and lipid metabolism in adipose tissue, endothelial cell and hepatocyte cultures in a modular bioreactor.

机构信息

Centro Interdipartimentale di Ricerca E. Piaggio, Faculty of Engineering, University of Pisa, Pisa, Italy.

出版信息

Biotechnol J. 2010 Jun;5(6):618-26. doi: 10.1002/biot.201000009.

DOI:10.1002/biot.201000009
PMID:20518065
Abstract

Static cell culture has serious limitations in its ability to represent cellular behaviour within a live organism. In vivo, cells are constantly exposed to the flow of bodily fluids and contact with other cell types. Bioreactors provide the opportunity to study cells in an environment that more closely resembles the in vivo setting because cell cultures can be exposed to dynamic flow in contact with or in proximity to other cell types. In this study we compared the metabolic profile of a dynamic cell culture system to that of a static cell culture in three different cellular phenotypes: adipocytes, endothelial cells and hepatocytes. Albumin, glucose, free fatty acids, glycerol, and lactate were measured over 48 h. We show that all three cell types have increased glucose uptake in the presence of flow; lactate release was also significantly affected. We provide robust evidence that the presence of flow significantly modifies cellular metabolism. While flow provides a more uniform nutrient distribution and increases metabolite turnover, our results indicate that different cell types have specific metabolic responses to flow, suggesting cell-specific flow-regulated activation of metabolite signalling pathways.

摘要

静态细胞培养在其代表活体组织中细胞行为的能力方面存在严重的局限性。在体内,细胞不断受到体液流动和与其他细胞类型接触的影响。生物反应器为研究细胞提供了机会,使细胞在更接近体内环境的条件下进行培养,因为细胞培养物可以在与其他细胞类型接触或接近的情况下暴露于动态流动中。在这项研究中,我们将动态细胞培养系统的代谢谱与三种不同细胞表型(脂肪细胞、内皮细胞和肝细胞)的静态细胞培养进行了比较。在 48 小时内测量了白蛋白、葡萄糖、游离脂肪酸、甘油和乳酸的含量。我们发现,所有三种细胞类型在有流动的情况下都增加了葡萄糖的摄取;乳酸的释放也受到了显著影响。我们提供了有力的证据表明,流动的存在显著改变了细胞的代谢。虽然流动提供了更均匀的营养分布并增加了代谢物的周转率,但我们的结果表明,不同的细胞类型对流动有特定的代谢反应,这表明细胞特异性的流动调节激活了代谢物信号通路。

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