Metabolic Patterning on a Chip: Towards in vitro Liver Zonation of Primary Rat and Human Hepatocytes.
Metabolic Patterning on a Chip: Towards in vitro Liver Zonation of Primary Rat and Human Hepatocytes.
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DOI：
10.1038/s41598-018-27179-6
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发表时间：
2018-06-12
影响因子：
4.6
通讯作者：
Usta OB
中科院分区：
文献类型：
--
作者：
Kang YBA;Eo J;Mert S;Yarmush ML;Usta OB
许多重要的健康和患病组织在整个组织中的代谢能力显示出空间差异。肝脏是这种异质性的一个主要例子，在这种情况下，跨越肝窦的各种代谢活动的逐渐变化被称为肝脏的“带状”。在这里，我们介绍了芯片上的代谢模式(MPOC)平台，该平台能够通过各种代谢调节剂(如激素和诱导剂)的主动增强梯度，动态地创建跨越肝组织微腔长度的代谢模式。利用这个平台，我们能够创造出具有逐渐变化的代谢活动的大鼠和人类来源的连续肝组织。我们在氮、碳水化合物和外源代谢中创建的梯度概括了体内类似分区和分区毒性反应的情况。除了我们在这里演示的在体外重述肝脏分区的应用之外，MPOC平台还可以用于各种目的和扩展，包括更好地了解发育和成体阶段许多不同组织中的异质性。
An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the liver sinusoid is termed as “zonation” of the liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers. Using this platform, we were able to create continuous liver tissues of both rat and human origin with gradually changing metabolic activities. The gradients we have created in nitrogen, carbohydrate and xenobiotic metabolisms recapitulated an in vivo like zonation and zonal toxic response. Beyond its application in recapitulation of liver zonation in vitro as we demonstrate here, the MPOC platform can be used and expanded for a variety of purposes including better understanding of heterogeneity in many different tissues during developmental and adult stages.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
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