Tailoring mathematical models to stem-cell derived cardiomyocyte lines can improve predictions of drug-induced changes to their electrophysiology

Lei, C. L. et al. (2017) Tailoring mathematical models to stem-cell derived cardiomyocyte lines can improve predictions of drug-induced changes to their electrophysiology. Frontiers in Physiology, 8, 986. (doi: 10.3389/fphys.2017.00986) (PMID:29311950) (PMCID:PMC5732978)

Abstract

Human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) have applications in disease modeling, cell therapy, drug screening and personalized medicine. Computational models can be used to interpret experimental findings in iPSC-CMs, provide mechanistic insights, and translate these findings to adult cardiomyocyte (CM) electrophysiology. However, different cell lines display different expression of ion channels, pumps and receptors, and show differences in electrophysiology. In this exploratory study, we use a mathematical model based on iPSC-CMs from Cellular Dynamic International (CDI, iCell), and compare its predictions to novel experimental recordings made with the Axiogenesis Cor.4U line. We show that tailoring this model to the specific cell line, even using limited data and a relatively simple approach, leads to improved predictions of baseline behavior and response to drugs. This demonstrates the need and the feasibility to tailor models to individual cell lines, although a more refined approach will be needed to characterize individual currents, address differences in ion current kinetics, and further improve these results.

• Item Type: Articles
• Additional Information: CL acknowledges support from the Clarendon Scholarship Fund, the Engineering and Physical Sciences Research Council (EPSRC) and the Medical Research Council (MRC) (Grant Number EP/L016044/1). KW was supported by a Roche Post-doctoral Fellowship. MC and DG acknowledge support from BBSRC grant BB/P010008/1. This work was supported by the Wellcome Trust [grant number 101222/Z/13/Z]: GM gratefully acknowledges support from a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Godfrey
• Authors: Lei, C. L., Wang, K., Clerx, M., Johnstone, R. H., Hortigon-Vinagre, M. P., Zamora, V., Allan, A., Smith, G. L., Gavaghan, D. J., Mirams, G. R., and Polonchuk, L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Frontiers in Physiology
• Publisher: Frontiers Media
• ISSN: 1664-042X
• ISSN (Online): 1664-042X
• Copyright Holders: Copyright © 2017 Lei, Wang, Clerx, Johnstone, Hortigon-Vinagre, Zamora, Allan, Smith, Gavaghan, Mirams and Polonchuk
• First Published: First published in Frontiers in Physiology 8:986
• Publisher Policy: Reproduced under a Creative Commons license