دورية أكاديمية
Stem cell models as an in vitro model for predictive toxicology.
| العنوان: | Stem cell models as an in vitro model for predictive toxicology. |
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| المؤلفون: | Lynch S; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, U.K., Pridgeon CS; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, U.K., Duckworth CA; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, U.K., Sharma P; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, U.K., Park BK; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, U.K., Goldring CEP; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, U.K. C.E.P.Goldring@liverpool.ac.uk. |
| المصدر: | The Biochemical journal [Biochem J] 2019 Apr 15; Vol. 476 (7), pp. 1149-1158. Date of Electronic Publication: 2019 Apr 15. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Published by Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 2984726R Publication Model: Electronic Cited Medium: Internet ISSN: 1470-8728 (Electronic) Linking ISSN: 02646021 NLM ISO Abbreviation: Biochem J Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society |
| مواضيع طبية MeSH: | Drug-Related Side Effects and Adverse Reactions*, Stem Cells/*drug effects, Animals ; Gastrointestinal Tract/drug effects ; Heart/drug effects ; Humans ; Liver/drug effects ; Models, Biological ; Toxicological Phenomena |
| مستخلص: | Adverse drug reactions (ADRs) are the unintended side effects of drugs. They are categorised as either predictable or unpredictable drug-induced injury and may be exhibited after a single or prolonged exposure to one or multiple compounds. Historically, toxicology studies rely heavily on animal models to understand and characterise the toxicity of novel compounds. However, animal models are imperfect proxies for human toxicity and there have been several high-profile cases of failure of animal models to predict human toxicity e.g. fialuridine, TGN1412 which highlight the need for improved predictive models of human toxicity. As a result, stem cell-derived models are under investigation as potential models for toxicity during early stages of drug development. Stem cells retain the genotype of the individual from which they were derived, offering the opportunity to model the reproducibility of rare phenotypes in vitro Differentiated 2D stem cell cultures have been investigated as models of hepato- and cardiotoxicity. However, insufficient maturity, particularly in the case of hepatocyte-like cells, means that their widespread use is not currently a feasible method to tackle the complex issues of off-target and often unpredictable toxicity of novel compounds. This review discusses the current state of the art for modelling clinically relevant toxicities, e.g. cardio- and hepatotoxicity, alongside the emerging need for modelling gastrointestinal toxicity and seeks to address whether stem cell technologies are a potential solution to increase the accuracy of ADR predictivity in humans. (© 2019 The Author(s).) |
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| معلومات مُعتمدة: | MR/L006758/1 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Keywords: cardiotoxicity; gastrointestinal toxicity; hepatotoxicity; organoid; stem cell; toxicology |
| تواريخ الأحداث: | Date Created: 20190417 Date Completed: 20200210 Latest Revision: 20210109 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6463389 |
| DOI: | 10.1042/BCJ20170780 |
| PMID: | 30988136 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1470-8728 |
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| DOI: | 10.1042/BCJ20170780 |