A human liver organoid screening platform for DILI risk prediction

Cj, Zhang; Meyer, Sophia R.; O’Meara, Matthew J.; Capeling, Meghan M.; Ferrer-Torres, Daysha; Childs, Charlie J.; Spence, Jason R.; Fontana, Robert J.; Sexton, Jonathan Z.

doi:10.1016/j.jhep.2023.01.019

Cited by 40 publications

(32 citation statements)

References 47 publications

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“…Additionally, transcriptomics with morphological profiling was used to predict other synergistic toxicities. Overall, the study highlights the potential of liver organoids as a promising model for DILI risk prediction and emphasizes the need for further optimization and expansion to encompass patient genetic diversity (Ahmed et al, 2022f;Zhang et al, 2023).…”

Section: Toxicity and Organ On Chipmentioning

confidence: 94%

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

et al. 2023

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The inefficiency of existing animal models to precisely predict human pharmacological effects is the root reason for drug development failure. Microphysiological system/organ-on-a-chip technology (organ-on-a-chip platform) is a microfluidic device cultured with human living cells under specific organ shear stress which can faithfully replicate human organ-body level pathophysiology. This emerging organ-on-chip platform can be a remarkable alternative for animal models with a broad range of purposes in drug testing and precision medicine. Here, we review the parameters employed in using organ on chip platform as a plot mimic diseases, genetic disorders, drug toxicity effects in different organs, biomarker identification, and drug discoveries. Additionally, we address the current challenges of the organ-on-chip platform that should be overcome to be accepted by drug regulatory agencies and pharmaceutical industries. Moreover, we highlight the future direction of the organ-on-chip platform parameters for enhancing and accelerating drug discoveries and personalized medicine.

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Section: Toxicity and Organ On Chipmentioning

confidence: 94%

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

et al. 2023

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“…DILI is one of the most frequent reasons for the failure of new drugs in clinical trials, mainly as a result of the poor predictive nature of the animal methods used in its evaluation. 56,57 There are many more examples of this type of failing, all of which constitute substantial evidence for a paradigm shift in how we should approach research and testing.…”

Section: An Overview Of the Three Rs And The Case For Changementioning

confidence: 99%

It’s Time to Review the Three Rs, to Make them More Fit for Purpose in the 21st Century

Bailey

2024

Altern Lab Anim

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The Three Rs have become widely accepted and pursued, and are now the go-to framework that encourages the humane use of animals in science, where no other option is believed to exist. However, many people, including scientists, harbour varying degrees of concern about the value and impact of the Three Rs. This ranges from a continued adherence to the Three Rs principles in the belief that they have performed well, through a belief that there should be more emphasis (or indeed a sole focus) on replacement, to a view that the principles have hindered, rather than helped, a critical approach to animal research that should have resulted in replacement to a much greater extent. This critical review asks questions of the Three Rs and their implementation, and provides an overview of the current situation surrounding animal use in biomedical science (chiefly in research). It makes a case that it is time to move away from the Three Rs and that, while this happens, the principles need to be made more robust and enforced more efficiently. To expedite a shift from animal use in science, toward a much greater and quicker adoption of human-specific New Approach Methodologies (NAMs), some argue for a straightforward focus on the best available science.

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“…Bouwmeester et al 249 established hepatocytelike ICOs and detected the expression and activity of drug metabolism-related genes to confirm the ability of organoids in ex vivo toxicity assessment. Zhang et al 250 developed a high throughput screening platform based on the human liver organoid-on-a-chip for drug-induced liver injury that pooled multiomics such as biomarker/analyte detection, high-content imaging-enabled phenotyping, and single-cell RNA sequencing. The authors demonstrate the effectiveness of this platform by testing a set of known hepatotoxic drugs and comparing the results to clinical data.…”

Section: Drug Researchmentioning

confidence: 99%

Organoids: The current status and biomedical applications

Yang

Kung

et al. 2023

MedComm

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Organoids are three‐dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long‐term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large‐scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

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A human liver organoid screening platform for DILI risk prediction

Cited by 40 publications

References 47 publications

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

It’s Time to Review the Three Rs, to Make them More Fit for Purpose in the 21st Century

Organoids: The current status and biomedical applications

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