Increasing Predictivity in Toxicity and Safety Pharmacology
Applying Relevant Human Model Cells
The toxicity and safety assessment of new pharmaceuticals and chemicals is a complex process that incorporates information from in silico analyses, in vitro studies, and animal testing. Over the past decade there has been an growing need for validated, physiologically relevant, and predictive human model cells. Several factors have contributed to this need:
- High attrition rate of new drugs in development (Kola, I and Landis, J, 2004)
- Withdrawal of marketed drugs due to unforeseen toxicity (Qureshi, ZP, et al. 2011)
- Increased focus on animal welfare issues due, in part, to legislative changes.
iCell® and MyCell® Products offer a novel approach to in vitro safety testing that overcomes many limitations of existing models. Some of the benefits include:
- Biological relevance – human cell models
- Purity – ensures reproducible and consistent results
- Scalability – our production process allows for large number of cells that eliminate the need for repeat sourcing and validation
The importance of iCell and MyCell products to the field of safety assessment is best evidenced by a proposed new regulatory paradigm (Gintant G, Sager PT, Stockbridge N, 2016, Sager PT, et al., 2014) to validate and standardize the use of stem cell-derived cardiomyocytes in in vitro assays for predicting cardiac arrhythmia.
Browse the growing list of publications that demonstrate the use of iCell human model cells for interrogating mechanisms of toxicity and improving predictivity:
- Lamore SD, et al. (2017) Deconvoluting Kinase Inhibitor Induced Cardiotoxicity. Toxicol Sci. [Epub ahead of print].
- Necela, BM, et al. (2017) The Antineoplastic Drug, Trastuzumab, Dysregulates Metabolism in iPSC-derived Cardiomyocytes. Clin Transl Med. 6: 5.
- Gao X, Liu Y. (2017) A Transcriptomic Study Suggesting Human iPSC-derived Hepatocytes Potentially Offer a Better in Vitro Model of Hepatotoxicity than Most Hepatoma Cell Lines. Cell Biol Toxicol. [Epub ahead of print]
- Huo J, et al. (2017) Evaluation of Batch Variations in Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes from 2 Major Suppliers. Toxicol Sci. Mar 1;156(1):25-38.
- Ando H. (2017) A New Paradigm for Drug-induced Torsadogenic Risk Assessment using Human iPS cell-derived Cardiomyocytes. J Pharmacol Toxicol Methods. 84:111-127.
- Lagrutta A. (2016) Interaction between Amiodarone and Hepatitis-C Virus Nucleotide Inhibitors in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes and HEK-293 Cav1.2 Over-expressing Cells. Toxicol Appl Pharmacol. 308:66-76.
- Millard DC (2016) Identification of Drug-Drug Interactions In Vitro: A Case Study Evaluating the Effects of Sofosbuvir and Amiodarone on hiPSC-Derived Cardiomyocytes. Toxicol Sci. 154(1):174-182.