In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

Wen, Xiaopeng; Yoshimoto, Koki; Yamanaka, Makoto; Terada, Shiho; Kamei, Ken‐ichiro

doi:10.1016/j.ooc.2021.100010

Cited by 5 publications

(6 citation statements)

References 40 publications

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“…Recently, we reported the multilayered GLA-MPS 27,73 to realize both individual accessibility for each tissue and closed loop medium circulation, for recapitulating inflammatory bowel disease by treating intestinal cells with an inflammatory inducer (e.g., lipopolysaccharide). However, the multilayered GLA-MPS device was made of PDMS and was not suitable for modeling NAFLD without any surface treatment against molecular absorption, such as FFAs 28 . As shown in Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Free fatty acids (FFAs) are a critical factor in NAFLD. Although PDMS-based microfluidic cell culture systems 25,26 , including our previously reported in vitro GLA model 27 , solve the aforementioned issues of OOCs for GLA, PDMS-based platforms without any treatments for preventing the absorption of hydrophobic molecules are not applicable for recapitulating NAFLD 28 .…”

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confidence: 99%

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Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

et al. 2023

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Non-alcoholic fatty liver disease (NAFLD) afflicts a significant percentage of the population; however, no effective treatments have yet been established because of the unsuitability of in vitro assays and animal experimental models. Here, we present an integrated-gut-liver-on-a-chip (iGLC) platform as an in vitro human model of the gut-liver axis (GLA) by co-culturing human gut and liver cell lines interconnected via microfluidics in a closed circulation loop, for the initiation and progression of NAFLD by treatment with free fatty acids (FFAs) for 1 and 7 days, respectively. Co-cultured Caco-2 gut-mimicking cells and HepG2 hepatocyte-like cells demonstrate the protective effects from apoptosis against FFAs treatment, whereas mono-cultured cells exhibit induced apoptosis. Phenotype and gene expression analyses reveal that the FFAs-treated gut and liver cells accumulated intracellular lipid droplets and show an increase in gene expression associated with a cellular response to copper ions and endoplasmic reticulum stress. As an in vitro human GLA model, the iGLC platform may serve as an alternative to animal experiments for investigating the mechanisms of NAFLD.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

et al. 2023

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“…In addition to its transparency and biocompatibility, COC exhibits no/low absorption of chemicals and is approved by Food and Drug Administration (FDA) [ 51 , 52 ]. Despite these interesting properties, the COC devices are not widely used in cell culture [ 53 , 54 , 55 ]. The current work aims to develop standardized COC bioreactor using process adapted to mass production and to validate its use for cell culture.…”

Section: Discussionmentioning

confidence: 99%

Validation of HepG2/C3A Cell Cultures in Cyclic Olefin Copolymer Based Microfluidic Bioreactors

et al. 2022

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Organ-on-chip (OoC) technology is one of the most promising in vitro tools to replace the traditional animal experiment-based paradigms of risk assessment. However, the use of OoC in drug discovery and toxicity studies remain still limited by the low capacity for high-throughput production and the incompatibility with standard laboratory equipment. Moreover, polydimethylsiloxanes, the material of choice for OoC, has several drawbacks, particularly the high absorption of drugs and chemicals. In this work, we report the development of a microfluidic device, using a process adapted for mass production, to culture liver cell line in dynamic conditions. The device, made of cyclic olefin copolymers, was manufactured by injection moulding and integrates Luer lock connectors compatible with standard medical and laboratory instruments. Then, the COC device was used for culturing HepG2/C3a cells. The functionality and behaviour of cultures were assessed by albumin secretion, cell proliferation, viability and actin cytoskeleton development. The cells in COC device proliferated well and remained functional for 9 days of culture. Furthermore, HepG2/C3a cells in the COC biochips showed similar behaviour to cells in PDMS biochips. The present study provides a proof-of-concept for the use of COC biochip in liver cells culture and illustrate their potential to develop OoC.

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“…156 Similarly, Wen et al demonstrated the use of COP for modeling a nonalcoholic fatty liver disease microphysiological system. 157 The majority of microfluidic devices fabricated in laboratories required expensive equipment, which becomes difficult for all institutions to afford. COCbased microfluidic devices can be fabricated easily on a wide scale for commercial purposes.…”

Section: Poly(methyl Methacrylate)mentioning

confidence: 99%

Advances in Organ-on-a-Chip Materials and Devices

Nahak¹,

Mishra²,

Preetam³

et al. 2022

ACS Appl. Bio Mater.

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The organ-on-a-chip (OoC) paves a way for biomedical applications ranging from preclinical to clinical translational precision. The current trends in the in vitro modeling is to reduce the complexity of human organ anatomy to the fundamental cellular microanatomy as an alternative of recreating the entire cell milieu that allows systematic analysis of medicinal absorption of compounds, metabolism, and mechanistic investigation. The OoC devices accurately represent human physiology in vitro; however, it is vital to choose the correct chip materials. The potential chip materials include inorganic, elastomeric, thermoplastic, natural, and hybrid materials. Despite the fact that polydimethylsiloxane is the most commonly utilized polymer for OoC and microphysiological systems, substitute materials have been continuously developed for its advanced applications. The evaluation of human physiological status can help to demonstrate using noninvasive OoC materials in real-time procedures. Therefore, this Review examines the materials used for fabricating OoC devices, the application-oriented pros and cons, possessions for device fabrication and biocompatibility, as well as their potential for downstream biochemical surface alteration and commercialization. The convergence of emerging approaches, such as advanced materials, artificial intelligence, machine learning, three-dimensional (3D) bioprinting, and genomics, have the potential to perform OoC technology at next generation. Thus, OoC technologies provide easy and precise methodologies in cost-effective clinical monitoring and treatment using standardized protocols, at even personalized levels. Because of the inherent utilization of the integrated materials, employing the OoC with biomedical approaches will be a promising methodology in the healthcare industry.

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In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

Cited by 5 publications

References 40 publications

Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

Validation of HepG2/C3A Cell Cultures in Cyclic Olefin Copolymer Based Microfluidic Bioreactors

Advances in Organ-on-a-Chip Materials and Devices

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