A vascular-liver chip for sensitive detection of nutraceutical metabolites from human pluripotent stem cell derivatives

Yu, Fang; Goh, Yeek Teck; Li, Huan; Narmada, Balakrishnan Chakrapani; Ni, Ming; Xu, Guo Lin; Hsieh, Tseng Ming; Toh, Yi‐Chin; Cheung, Christine; Iliescu, Ciprian; Yu, Hanry

doi:10.1063/5.0004286

Cited by 12 publications

(4 citation statements)

References 60 publications

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“…In a follow-up study, the same microfluidic culture was used to mimic liver zonation based on the formation of an oxygen gradient in the biochip ( Danoy et al, 2020 ). Moreover, when co-cultured iPSC-derived endothelial cells, iPSC-derived HLCs were able to metabolize quercetin into its active metabolites ( Yu et al, 2020 ).…”

Section: Liver In Vitro Models For Toxicological Smentioning

confidence: 99%

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

Serras

Rodrigues

Cipriano

et al. 2021

Front. Cell Dev. Biol.

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The poor predictability of human liver toxicity is still causing high attrition rates of drug candidates in the pharmaceutical industry at the non-clinical, clinical, and post-marketing authorization stages. This is in part caused by animal models that fail to predict various human adverse drug reactions (ADRs), resulting in undetected hepatotoxicity at the non-clinical phase of drug development. In an effort to increase the prediction of human hepatotoxicity, different approaches to enhance the physiological relevance of hepatic in vitro systems are being pursued. Three-dimensional (3D) or microfluidic technologies allow to better recapitulate hepatocyte organization and cell-matrix contacts, to include additional cell types, to incorporate fluid flow and to create gradients of oxygen and nutrients, which have led to improved differentiated cell phenotype and functionality. This comprehensive review addresses the drug-induced hepatotoxicity mechanisms and the currently available 3D liver in vitro models, their characteristics, as well as their advantages and limitations for human hepatotoxicity assessment. In addition, since toxic responses are greatly dependent on the culture model, a comparative analysis of the toxicity studies performed using two-dimensional (2D) and 3D in vitro strategies with recognized hepatotoxic compounds, such as paracetamol, diclofenac, and troglitazone is performed, further highlighting the need for harmonization of the respective characterization methods. Finally, taking a step forward, we propose a roadmap for the assessment of drugs hepatotoxicity based on fully characterized fit-for-purpose in vitro models, taking advantage of the best of each model, which will ultimately contribute to more informed decision-making in the drug development and risk assessment fields.

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Section: Liver In Vitro Models For Toxicological Smentioning

confidence: 99%

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

Serras

Rodrigues

Cipriano

et al. 2021

Front. Cell Dev. Biol.

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“…The effectiveness of the GI barrier was verified by assessing the permeability of three prominent drugs, namely caffeine, mannitol, and propranolol, alongside control Caco-2 cells. A perfusion incubator device was used by Yu et al 181 to develop a liver-vascular co-culture platform for analyzing the metabolism of nutraceutical compounds. The co-culture setup was made of a concurrent culturing chamber that contains 3D hepatocytes, HPS-derived hepatocyte spheroids (on the bottom), and the HPS-derived endothelial cells (on top).…”

Section: Multi-organ-on-a-chipmentioning

confidence: 99%

Recent advances and future prospects of functional organ-on-a-chip systems

Moghaddam

Davachi

et al. 2022

Mater. Chem. Front.

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“…A longstanding technological approach involves using glass or glass-silicon fabricated devices. The hydrophilicity of such devices ensures little absorption of proteins, drugs, and metabolites [23,24]. Furthermore, agarose is known to be non-adhesive and suitable for spheroid formation by cell-cell interactions [25].…”

Section: Technological Approaches For Tumor-on-chip Technology 221 Advances In Microfluidic Technologiesmentioning

confidence: 99%

Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside

Bērziņa

Harrison

Taly

et al. 2021

Cancers

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Tumor-on-chip technology has cemented its importance as an in vitro tumor model for cancer research. Its ability to recapitulate different elements of the in vivo tumor microenvironment makes it promising for translational medicine, with potential application in enabling personalized anti-cancer therapies. Here, we provide an overview of the current technological advances for tumor-on-chip generation. To further elevate the functionalities of the technology, these approaches need to be coupled with effective analysis tools. This aspect of tumor-on-chip technology is often neglected in the current literature. We address this shortcoming by reviewing state-of-the-art on-chip analysis tools for microfluidic tumor models. Lastly, we focus on the current progress in tumor-on-chip devices using patient-derived samples and evaluate their potential for clinical research and personalized medicine applications.

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A vascular-liver chip for sensitive detection of nutraceutical metabolites from human pluripotent stem cell derivatives

Abstract: A vascular-liver chip for sensitive detection of nutraceutical metabolites from human pluripotent stem cell derivatives

Cited by 12 publications

References 60 publications

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

Recent advances and future prospects of functional organ-on-a-chip systems

Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside

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