Engineering Microfluidic Organoid-on-a-Chip Platforms

Yu, Fang; Hunziker, Walter; Choudhury, Deepak

doi:10.3390/mi10030165

Cited by 171 publications

(133 citation statements)

References 64 publications

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“…The animal cell line‐based models have inherent limitations for the construction of a physiologically realistic human model. Recently, stem cells and primary cell culture technology have progressed and organoid‐based systems are emerging (Yu, Hunziker, & Choudhury, ). They will help overcome the limitations of cell lines and provide a physiologically more realistic model.…”

Section: Discussionmentioning

confidence: 99%

Construction of pancreas–muscle–liver microphysiological system (MPS) for reproducing glucose metabolism

Lee

Choi

et al. 2019

Biotech & Bioengineering

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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. K E Y W O R D Sglucose metabolism, mathematical model, multiorgan MPS, multiorgan-on-a-chip (MOC), pancreas-muscle-liver MPS

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Section: Discussionmentioning

confidence: 99%

Construction of pancreas–muscle–liver microphysiological system (MPS) for reproducing glucose metabolism

Lee

Choi

et al. 2019

Biotech & Bioengineering

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“…Organ-on-chip systems can also be equipped with diverse sensors and actuators and integrated with them, so that they can more accurately monitor and control key parameters in the human body, various physical and electrical stimuli, nutrition exchange, etc. [19].…”

Section: Microfabricationmentioning

confidence: 99%

Application of Organ-on-Chip in Drug Discovery

Zhu¹

2020

JBM

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Nowadays the pharmaceutical industry is facing long and expensive drug discovery processes. Current preclinical drug evaluation strategies that utilize oversimplified cell cultures and animal models cannot satisfy the growing demand for new and effective drugs. The microengineered biomimetic system, namely organ-on-chip (OOC), simulating both the biology and physiology of human organs, has shown greater advantages than traditional models in drug efficacy and safety evaluation. The microengineered co-culture models recapitulate the complex interactions between different types of cells in vivo. Organ-on-chip system has also avoided the substantial interspecies differences in key disease pathways and disease-induced changes in gene expression profiles between human and other animal models. Biomimetic microsystems representing different organs have been integrated into a single microdevice and linked by a microfluidic circulatory system in a physiologically relevant manner. In this review, I outline the current development of organon-chip, and their applications in drug discovery. This human-on-chip system can model the complex, dynamic process of drug absorption, distribution, metabolism and excretion, and more reliably evaluate drug efficacy and toxicity. I also discuss, for the next generation of organ-on-chip, more research is required to identify suitable materials that can be used to mass produce organs-on-chips at low cost, and to scale up the system to be suitable for high-throughput analysis and commercial applications. There are more aspects that need to be further studied, thereby bring a much better tool to patients, drug developers, and clinicians.

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“…Accordingly, organoids represent a major improvement in disease modeling compared to animal models, as they overcome ethical issues, are more cost-effective and allow faster analysis [144,145]. Since the development of the first intestinal organoids by Sato and collaborators in 2009 [146], many other models of various tissues have been developed following diverse approaches such as (i) Matrigel scaffold-based, (ii) Embryoid Bodies (EB)-based, and (iii) Air-Liquid Interface (ALI) method [147], and they have been used to model a great range of pathologies, from viral infection to solid cancers, cystic fibrosis, and endometriosis ( Table 5). Even if in the last decade efforts have been made for improving organoids fidelity to the in vivo counterpart [148], there are still several critical aspects that have to be taken into account when evaluating organoids predictability.…”

Section: Ex Vivo Stem Cell-based Systems: Organoidsmentioning

confidence: 99%

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

Argentati

Tortorella

Bazzucchi

et al. 2020

JPM

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Ex vivo cell/tissue-based models are an essential step in the workflow of pathophysiology studies, assay development, disease modeling, drug discovery, and development of personalized therapeutic strategies. For these purposes, both scientific and pharmaceutical research have adopted ex vivo stem cell models because of their better predictive power. As matter of a fact, the advancing in isolation and in vitro expansion protocols for culturing autologous human stem cells, and the standardization of methods for generating patient-derived induced pluripotent stem cells has made feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Furthermore, the potential of stem cells on generating more complex systems, such as scaffold-cell models, organoids, or organ-on-a-chip, allowed to overcome the limitations of the two-dimensional culture systems as well as to better mimic tissues structures and functions. Finally, the advent of genome-editing/gene therapy technologies had a great impact on the generation of more proficient stem cell-disease models and on establishing an effective therapeutic treatment. In this review, we discuss important breakthroughs of stem cell-based models highlighting current directions, advantages, and limitations and point out the need to combine experimental biology with computational tools able to describe complex biological systems and deliver results or predictions in the context of personalized medicine.Since their establishment, cell cultures have been proven to be the first and most powerful tool for the in vitro investigation of cell biology, from basic research to more complex translational approaches [6]. Classical two-dimensional (2D)-cultures usually consist of a unique type of cells (primary or continuous cultures) that grow in tissue culture polystyrene as adherent monolayers or in floating suspension, both in culture media that provide essential nutrients and growth factors. 2D-strategies are widely used to obtain a large number of cells, thus allowing the in vitro study of molecular mechanisms and development of metabolic assays [7-9]. However, due to their inability to recreate the in vivo complexity of the biological environment, they are not suitable for accurate disease modeling. These limitations have been overcome by the development of three-dimensional (3D)-cell cultures systems [10]. The rationale design of 3D-cell cultures is to harvest cells in microstructures that resemble tissues or organs shape and organization, thus allowing better cell-to-cell/cell-environment contacts and signaling crosstalk [11][12][13][14][15], essential events for tissues correct development and functioning [14,15]. The 3D-cell culture strategy is articulated in many different methods and techniques that can be grouped in scaffold-based or non-scaffold based platforms, each with particular advantages and disadvantages that make them useful for different applications [10,[16][17][18][19]. 3D-cell culture strategies are supported by the in silico...

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Engineering Microfluidic Organoid-on-a-Chip Platforms

Cited by 171 publications

References 64 publications

Construction of pancreas–muscle–liver microphysiological system (MPS) for reproducing glucose metabolism

Construction of pancreas–muscle–liver microphysiological system (MPS) for reproducing glucose metabolism

Application of Organ-on-Chip in Drug Discovery

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

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