title: Toxicity testing and drug screening using iPSC-derived hepatocytes, cardiomyocytes, and neural cells.
abstract: Unexpected toxicity in areas such as cardiotoxicity, hepatotoxicity, and neurotoxicity is a serious complication of clinical therapy and one of the key causes for failure of promising drug candidates in development. Animal studies have been widely used for toxicology research to provide preclinical security evaluation of various therapeutic agents under development. Species differences in drug penetration of the blood-brain barrier, drug metabolism, and related toxicity contribute to failure of drug trials from animal models to human. The existing system for drug discovery has relied on immortalized cell lines, animal models of human disease, and clinical trials in humans. Moreover, drug candidates that are passed as being safe in the preclinical stage often show toxic effects during the clinical stage. Only around 16% drugs are approved for human use. Research on induced pluripotent stem cells (iPSCs) promises to enhance drug discovery and development by providing simple, reproducible, and economically effective tools for drug toxicity screening under development and, on the other hand, for studying the disease mechanism and pathways. In this review, we provide an overview of basic information about iPSCs, and discuss efforts aimed at the use of iPSC-derived hepatocytes, cardiomyocytes, and neural cells in drug discovery and toxicity testing.
authors.affiliation: a Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 4, 811 08 Bratislava, Slovak Republic.
authors.forename: Mária
authors.initials: M
authors.lastname: Csöbönyeiová
authors.affiliation: a Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 4, 811 08 Bratislava, Slovak Republic.
authors.forename: Štefan
authors.initials: Š
authors.lastname: Polák
authors.affiliation: b Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 4, 811 08 Bratislava, Slovak Republic.
authors.forename: L'uboš
authors.initials: L
authors.lastname: Danišovič
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations
keywords: cardiotoxicity; cardiotoxicité; criblage de medicaments; drug screening; hepatotoxicity; hepatotoxicité; iPSC; iPSCs; neurotoxicity; neurotoxicité