Department of Chemical Engineering, Hongik University, Seoul, Republic of Korea.
Department of Bionano Engineering, Hanyang University, Ansan, Republic of Korea.
Biotechnol Bioeng. 2019 Dec;116(12):3433-3445. doi: 10.1002/bit.27151. Epub 2019 Sep 2.
Although in vitro models are widely accepted experimental platforms, their physiological relevance is often severely limited. The limitation of current in vitro models is strongly manifested in case of diseases where multiple organs are involved, such as diabetes and metabolic syndrome. Microphysiological systems (MPS), also known as organ-on-a-chip technology, enable a closer approximation of the human organs and tissues, by recreating the tissue microenvironment. Multiorgan MPS, also known as multiorgan-on-a-chip or body-on-a-chip, offer the possibility of reproducing interactions between organs by connecting different organ modules. Here, we designed a three-organ MPS consisting of pancreas, muscle, and liver, to recapitulate glucose metabolism and homeostasis by constructing a mathematical model of glucose metabolism, based on experimental measurement of glucose uptake by muscle cells and insulin secretion by pancreas cells. A mathematical model was used to modify the MPS to improve the physiological relevance, and by adding the liver model in the mathematical model, physiological realistic glucose and insulin profiles were obtained. Our study may provide a methodological framework for developing multiorgan MPS for recapitulating the complex interaction between multiple organs.
尽管体外模型被广泛认为是实验平台，但它们的生理相关性往往受到严重限制。目前的体外模型的局限性在涉及多个器官的疾病中表现得尤为明显，如糖尿病和代谢综合征。微生理系统（MPS），也称为器官芯片技术，通过重建组织微环境，更接近人体器官和组织。多器官 MPS，也称为多器官芯片或体芯片，通过连接不同的器官模块，提供了再现器官之间相互作用的可能性。在这里，我们设计了一个由胰腺、肌肉和肝脏组成的三器官 MPS，通过构建基于肌肉细胞摄取葡萄糖和胰腺细胞分泌胰岛素的实验测量的葡萄糖代谢数学模型，来概括葡萄糖代谢和内稳态。使用数学模型来修改 MPS 以提高生理相关性，并通过在数学模型中添加肝脏模型，获得了生理现实的葡萄糖和胰岛素谱。我们的研究可能为开发用于概括多个器官之间复杂相互作用的多器官 MPS 提供了一种方法框架。
