Evidence map›Paper›PMID 26880940›Full record

ArticleStem cells international2016

High Content Analysis of Human Pluripotent Stem Cell Derived Hepatocytes Reveals Drug Induced Steatosis and Phospholipidosis.

Arvind Pradip, Daniella Steel, Susanna Jacobsson, Gustav Holmgren, Magnus Ingelman-Sundberg, Peter Sartipy, Petter Björquist, Inger Johansson, Josefina Edsbagge

Open access · goldAbstract read
In one paragraph

Article in Stem cells international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.7field-weighted citation impact, top 7% of its field
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

16 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. In Vitro Models for Studying Chronic Drug-Induced Liver Injury.International journal of molecular sciences · 2022
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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 at 5 institutions in 6 countries.

Arvind PradipTakara Bio Europe AB (Former Cellectis AB/Cellartis AB), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden; Novo Nordisk A/S, Stem Cell Development, 2880 Bagsværd, Denmark.
Daniella SteelTakara Bio Europe AB (Former Cellectis AB/Cellartis AB), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden; Horizon Discovery Ltd, 7100 Cambridge Research Park, Waterbeach, Cambridge CB25 9TL, UK.
Susanna JacobssonTakara Bio Europe AB (Former Cellectis AB/Cellartis AB), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden.
Gustav HolmgrenTakara Bio Europe AB (Former Cellectis AB/Cellartis AB), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden; Systems Biology Research Center, School of Bioscience, University of Skövde, 541 28 Skövde, Sweden.
Magnus Ingelman-SundbergDepartment of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Peter SartipyTakara Bio Europe AB (Former Cellectis AB/Cellartis AB), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden; Systems Biology Research Center, School of Bioscience, University of Skövde, 541 28 Skövde, Sweden; AstraZeneca R&D, GMD CVMD GMed, 431 83 Mölndal, Sweden.
Petter BjörquistTakara Bio Europe AB (Former Cellectis AB/Cellartis AB), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden; NovaHep AB, Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden.
Inger JohanssonDepartment of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Josefina EdsbaggeTakara Bio Europe AB (Former Cellectis AB/Cellartis AB), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden.
Takara (Sweden) · SECellectis (United States) · USKarolinska Institutet · SEPharmacoGenetics (China) · CNUniversity of Skövde · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatotoxicity is one of the most cited reasons for withdrawal of approved drugs from the market. The use of nonclinically relevant in vitro and in vivo testing systems contributes to the high attrition rates. Recent advances in differentiating human induced pluripotent stem cells (hiPSCs) into pure cultures of hepatocyte-like cells expressing functional drug metabolizing enzymes open up possibilities for novel, more relevant human cell based toxicity models. The present study aimed to investigate the use of hiPSC derived hepatocytes for conducting mechanistic toxicity testing by image based high content analysis (HCA). The hiPSC derived hepatocytes were exposed to drugs known to cause hepatotoxicity through steatosis and phospholipidosis, measuring several endpoints representing different mechanisms involved in drug induced hepatotoxicity. The hiPSC derived hepatocytes were benchmarked to the HepG2 cell line and generated robust HCA data with low imprecision between plates and batches. The different parameters measured were detected at subcytotoxic concentrations and the order of which the compounds were categorized (as severe, moderate, mild, or nontoxic) based on the degree of injury at isomolar concentration corresponded to previously published data. Taken together, the present study shows how hiPSC derived hepatocytes can be used as a platform for screening drug induced hepatotoxicity by HCA.

Identifiers

PMID26880940
PMCPMC4736406
OpenAlexW2227311619

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.