Evidence map›Paper›PMID 36057418›Full record

ArticleToxicology in vitro : an international journal published in association with BIBRA2022

Analysis of reproducibility and robustness of OrganoPlate® 2-lane 96, a liver microphysiological system for studies of pharmacokinetics and toxicological assessment of drugs.

Yuki Kato, Alicia Y Lim, Courtney Sakolish, Alan Valdiviezo, Haley L Moyer, Philip Hewitt, Piyush Bajaj, Gang Han, Ivan Rusyn

Abstract read
In one paragraph

Article in Toxicology in vitro : an international journal published in association with BIBRA, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yuki KatoDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA; Laboratory for Drug Discovery and Development, Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., Osaka 561-0825, Japan.
Alicia Y LimDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Courtney SakolishDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Alan ValdiviezoDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Haley L MoyerDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Philip HewittChemical and Preclinical Safety, Merck Healthcare KGaA, 64293 Darmstadt, Germany.
Piyush BajajGlobal Investigative Toxicology, Preclinical Safety, Sanofi USA, MA 01701, USA.
Gang HanDepartment of Epidemiology and Biostatistics, Texas A&M University, College Station, TX 77843, USA.
Ivan RusynDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA. Electronic address: irusyn@cvm.tamu.edu.

Funding

Single cell, multi-parametric high throughput platform to classify endocrine disruptor potential of mixturesP42ES027704 · NIEHS · TEXAS A&M UNIVERSITY · PI Ivan Rusyn · 2017 to 2026
$21.2M
Regulatory Science in Environmental Health and ToxicologyT32ES026568 · NIEHS · TEXAS A&M UNIVERSITY · PI Weihsueh A Chiu, Natalie M Johnson · 2016 to 2026
$3.8M
TEX-VAL: Texas A&M Tissue Chip Validation ConsortiumU24TR002633 · NCATS · TEXAS A&M UNIVERSITY · PI RUSYN, IVAN, STEPHAN, CLIFFORD C · 2018 to 2019
$3.0M
IMSD at Texas A&M University: Initiative for Maximizing Student Diversity in Biomedical SciencesT32GM135748 · NIGMS · TEXAS A&M UNIVERSITY · PI BRINKMEYER-LANGFORD, CANDICE L., CHIU, WEIHSUEH A · 2020 to 2024
$1.2M
NCATS NIH HHS U24 TR002633NIEHS NIH HHS P42 ES027704NIEHS NIH HHS T32 ES026568NIGMS NIH HHS T32 GM135748
6 · The paper itself

Abstract

Establishing the functionality, reproducibility, robustness, and reliability of microphysiological systems is a critical need for adoption of these technologies. A high throughput microphysiological system for liver studies was recently proposed in which induced pluripotent stem cell-derived hepatocytes (iHeps) and non-parenchymal cells (endothelial cells and THP-1 cells differentiated with phorbol 12-myristate 13-acetate into macrophage-like cells) were co-cultured in OrganoPlate® 2-lane 96 devices. The goal of this study was to evaluate this platform using additional cell types and conditions and characterize its utility and reproducibility. Primary human hepatocytes or iHeps, with and without non-parenchymal cells, were cultured for up to 17 days. Image-based cell viability, albumin and urea secretion into culture media, CYP3A4 activity and drug metabolism were assessed. The iHeps co-cultured with non-parenchymal cells demonstrated stable cell viability and function up to 17 days; however, variability was appreciable both within and among studies. The iHeps in monoculture did not form clusters and lost viability and function over time. The primary human hepatocytes in monoculture also exhibited low cell viability and hepatic function. Metabolism of various drugs was most efficient when iHeps were co-cultured with non-parenchymal cells. Overall, we found that the OrganoPlate® 2-lane 96 device, when used with iHeps and non-parenchymal cells, is a functional liver microphysiological model; however, the high-throughput nature of this model is somewhat dampened by the need for replicates to compensate for high variability.

Indexed as

Cytochrome P-450 CYP3APhorbolsAcetatesAlbuminsCells, CulturedCulture MediaEndothelial CellsHepatocytesHumansLiverMyristatesReproducibility of ResultsUreaAcetatesAlbuminsCulture MediaCytochrome P-450 CYP3AMyristatesPhorbolsUreaLiverTestingTissue chip

Identifiers

PMID36057418
PMCPMC10015056

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.