ArticleToxicological sciences : an official journal of the Society of Toxicology2015
MicroRNA-122: a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity.
Open access · bronzeAbstract readComparative Study
In one paragraph
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% of its field
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.
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.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The diagnostic role of miR-122 in drug-induced liver injury: A systematic review and meta-analysis.Medicine · 2018Pooled it
- The Role of MicroRNAs Carried by Extracellular Vesicles in Tumorigenesis Through Reprogramming the Mitochondrial Information Processing System.International journal of molecular sciences · 2026Review
- HIVIL: A humanNAM journal · 2025Article
- Circulating miRNA 122-5p Expression Predicts Mortality and Cardiovascular Events in Chronic Hemodialysis Patients: A Multicentric, Pilot, Prospective Study.Biomolecules · 2023Observational
- Mn-SOD alleviates methotrexate-related hepatocellular injury via GSK-3β affecting anti-oxidative stress of HO-1 and Drp1.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Endogenous ROS production in early differentiation state suppresses endoderm differentiation via transient FOXC1 expression.Cell death discovery · 2022Article
- Identification of miR-199a-5p, miR-214-3p and miR-99b-5p as Fibrosis-Specific Extracellular Biomarkers and Promoters of HSC Activation.International journal of molecular sciences · 2021Article
- Liver Organoids: Recent Developments, Limitations and Potential.Frontiers in medicine · 2021Review
- Functionality of primary hepatic non-parenchymal cells in a 3D spheroid model and contribution to acetaminophen hepatotoxicity.Archives of toxicology · 2020Article
- Bioprinted liver provides early insight into the role of Kupffer cells in TGF-β1 and methotrexate-induced fibrogenesis.PloS one · 2019Article
- Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study.The AAPS journal · 2018Article
- MicroRNAs as biomarkers for liver injury: Current knowledge, challenges and future prospects.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017Review
- Donor-Dependent and Other Nondefined Factors Have Greater Influence on the Hepatic Phenotype Than the Starting Cell Type in Induced Pluripotent Stem Cell Derived Hepatocyte-Like Cells.Stem cells translational medicine · 2017Article
- Role of miRNA and its potential as a novel diagnostic biomarker in drug-induced liver injury.European journal of clinical pharmacology · 2017Review
- Reduced SHARPIN and LUBAC Formation May Contribute to CCl₄- or Acetaminophen-Induced Liver Cirrhosis in Mice.International journal of molecular sciences · 2017Article
- Liver microRNAs: potential mediators and biomarkers for metabolic and cardiovascular disease?European heart journal · 2016Review
- Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes.Chemico-biological interactions · 2016Article
- Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- RETRACTED: CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver FailureGastroenterology · 2015Article
- Sensitive Periods for the Effect of Child Maltreatment on Psychopathology Symptoms in Adolescence.Complex psychiatryArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 8 institutions in 2 countries.
Richard KiaMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Lorna KellyMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Rowena L C Sison-YoungMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Fang ZhangMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Chris S PridgeonMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
James A HeslopMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Pete MetcalfeMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Neil R KitteringhamMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Melissa BaxterMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Sean HarrisonMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Neil A HanleyMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Zoë D BurkeMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Mike P StormMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Melanie J WelhamMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
David ToshMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Barbara Küppers-MuntherMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
Josefina EdsbaggeMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Philip J Starkey LewisMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Frank BonnerMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Ernie HarpurMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
James SidawayMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Joanne BowesMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Stephen W FenwickMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Hassan MalikMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.
Chris E P GoldringMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
B Kevin ParkMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9PT, UK Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK, Takara Bio Europe AB (former Cellartis), Arvid Wallgrens Backe 20, 413 46 Göteborg, Sweden, School of Life Sciences, The Systems Biology Research Centre, University of Skövde, Box 408, 541 28 Skövde, Sweden, MRC Centre for Regenerative Medicine, SCRM Building, The University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK, Newcastle University, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK Drug Safety and Metabolism, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK and North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Sherrington Buildings, Ashton Street, University of Liverpool, Liverpool L69 3GE, UK Stem Cells for Safer Medicines, 7th Floor, Southside, 105 Victoria Street, London SW1E 6QT, UK Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, UK Centre fo
University of Central Lancashire · GBUniversity of Liverpool · GBUniversity of Edinburgh · GBUniversity of Manchester · GBAstraZeneca (United Kingdom) · GBManchester Academic Health Science Centre · GBUniversity of Bath · GBUniversity of Skövde · SE
Funding
Biotechnology and Biological Sciences Research CouncilMedical Research Council G0700654Medical Research Council G1000417Medical Research Council G1000417/94909Medical Research Council MR/J006793/1Medical Research Council MR/L006758/1Wellcome Trust 088566
Abstract
Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury.
Indexed as
AcetaminophenAdenosine TriphosphateAgedCell DifferentiationCell SurvivalChemical and Drug Induced Liver InjuryCulture MediaDiclofenacDose-Response Relationship, DrugEmbryonic Stem CellsFemaleGenetic MarkersHepatocytesHep G2 CellsHumansInduced Pluripotent Stem CellsAcetaminophenAdenosine TriphosphateCulture MediaDiclofenacGenetic MarkersL-Lactate DehydrogenaseMicroRNAsMIRN122 microRNA, humanbridging biomarkercell-specific biomarkercytotoxicitydrug-induced liver injuryhepatocytesin vitro modelmicroRNA
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