Liver‐on‐a‐Chip Models of Fatty Liver Disease

Hassan, Shabir; Sebastian, Shikha; Maharjan, Sushila; Lesha, Ami; Carpenter, Anne M.; Liu, Xiuli; Xie, Xin; Livermore, Carol; Zhang, Yu Shrike; Zarrinpar, Ali

doi:10.1002/hep.31106

Cited by 84 publications

(58 citation statements)

References 31 publications

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“…Liver-on-a-chip platforms can mimic in vivo conditions by recapitulating the sinusoidal structure of this organ, maintaining high cell viability and cellular phenotypes, and emulating the functions of native tissues [ 16 ]. In this respect, several models have been developed and are available for studying liver disease progression, facilitating drug discovery, and enabling toxicity tests [ 99 ]. For instance, Lee et al [ 100 ] designed a liver test microfluidic platform using cell printing.…”

Section: Applications Of Microfluidic Devicesmentioning

confidence: 99%

Fabrication and Applications of Microfluidic Devices: A Review

Niculescu

Chircov

Bîrcă

et al. 2021

IJMS

350

208

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Microfluidics is a relatively newly emerged field based on the combined principles of physics, chemistry, biology, fluid dynamics, microelectronics, and material science. Various materials can be processed into miniaturized chips containing channels and chambers in the microscale range. A diverse repertoire of methods can be chosen to manufacture such platforms of desired size, shape, and geometry. Whether they are used alone or in combination with other devices, microfluidic chips can be employed in nanoparticle preparation, drug encapsulation, delivery, and targeting, cell analysis, diagnosis, and cell culture. This paper presents microfluidic technology in terms of the available platform materials and fabrication techniques, also focusing on the biomedical applications of these remarkable devices.

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Section: Applications Of Microfluidic Devicesmentioning

confidence: 99%

Fabrication and Applications of Microfluidic Devices: A Review

Niculescu

Chircov

Bîrcă

et al. 2021

IJMS

350

208

View full text Add to dashboard Cite

show abstract

“…In vitro liver models are critical tools for drug development and pathophysiological studies [14]. It was recently acknowledged that hepatocytes cultured as a 2D monolayer cannot mimic the complex microenvironment of cells in vivo, and thus cause significant discrepancies between in vitro and in vivo results [21].…”

Section: Resultsmentioning

confidence: 99%

“…Amongst these in vitro 3D cell cultures, hepatocytes have attracted substantial interest because of the Bioengineering 2021, 8, 88 2 of 12 high demand for reliable hepatic models in pharmaceutical and pathophysiological studies [12,13]. For instance, precise understanding of the hepatic metabolism and toxicity of a new drug candidate is critically important in drug development [14]. Moreover, 3D ECMs can modulate the fingerprint functions of hepatocytes, including albumin secretion, urea synthesis, cytochrome 450 (CYP450) activities, and metabolism of drugs [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Electrospun Microfibers Modulate Intracellular Amino Acids in Liver Cells via Integrin β1

et al. 2021

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Although numerous recent studies have shown the importance of polymeric microfibrous extracellular matrices (ECMs) in maintaining cell behaviors and functions, the mechanistic nexus between ECMs and intracellular activities is largely unknown. Nevertheless, this knowledge will be critical in understanding and treating diseases with ECM remodeling. Therefore, we present our findings that ECM microstructures could regulate intracellular amino acid levels in liver cells mechanistically through integrin β1. Amino acids were studied because they are the fundamental blocks for protein synthesis and metabolism, two vital functions of liver cells. Two ECM conditions, flat and microfibrous, were prepared and studied. In addition to characterizing cell growth, albumin production, urea synthesis, and cytochrome p450 activity, we found that the microfibrous ECM generally upregulated the intracellular amino acid levels. Further explorations showed that cells on the flat substrate expressed more integrin β1 than cells on the microfibers. Moreover, after partially blocking integrin β1 in cells on the flat substrate, the intracellular amino acid levels were restored, strongly supporting integrin β1 as the linking mechanism. This is the first study to report that a non-biological polymer matrix could regulate intracellular amino acid patterns through integrin. The results will help with future therapy development for liver diseases with ECM changes (e.g., fibrosis).

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“…Basically, the microarchitecture of the liver is mimicked by a polymeric scaffold that consists of hundreds of small channels [ 64 ]. The dimensions are such that when hepatocytes are seeded into these channels, they form a long donut-shaped arrangement that closely resembles the hepatic lobule that a microfluid containing various nutrients and oxygen can pass through to simulate blood flow [ 65 ]. A more complex system can be engineered by integrating NPCs in a vascular layer comprising endothelial cells and macrophages to a hepatic layer comprising stellate cells co-cultured with hepatocytes [ 66 ].…”

Section: In Vitro Cell Culture Models Of Non-alcoholic Fatty Livermentioning

confidence: 99%

In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal

Soret

Magusto

Housset

et al. 2020

JCM

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Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), represents the hepatic manifestation of obesity and metabolic syndrome. Due to the spread of the obesity epidemic, NAFLD is becoming the most common chronic liver disease and one of the principal indications for liver transplantation. However, no pharmacological treatment is currently approved to prevent the outbreak of NASH, which leads to fibrosis and cirrhosis. Preclinical research is required to improve our knowledge of NAFLD physiopathology and to identify new therapeutic targets. In the present review, we summarize advances in NAFLD preclinical models from cellular models, including new bioengineered platforms, to in vivo models, with a particular focus on genetic and dietary mouse models. We aim to discuss the advantages and limits of these different models.

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Liver‐on‐a‐Chip Models of Fatty Liver Disease

Cited by 84 publications

References 31 publications

Fabrication and Applications of Microfluidic Devices: A Review

Fabrication and Applications of Microfluidic Devices: A Review

Electrospun Microfibers Modulate Intracellular Amino Acids in Liver Cells via Integrin β1

In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal

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