AuthorsA. Tveito, K. H. Jæger, N. Huebsch, B. Charrez, A. G. Edwards, S. Wall and K. E. Healy
TitleInversion and computational maturation of drug response using human stem cell derived cardiomyocytes in microphysiological systems
AfilliationScientific Computing
Project(s)Center for Biomedical Computing (SFF)
StatusPublished
Publication TypeJournal Article
Year of Publication2018
JournalNature Scientific Reports
Volume8
Number17626
Date Published12/2018
PublisherSpringer Nature
Abstract

While cardiomyocytes differentiated from human induced pluripotent stems cells (hiPSCs) hold great promise for drug screening, the electrophysiological properties of these cells can be variable and immature, producing results that are significantly different from their human adult counterparts. Here, we describe a computational framework to address this limitation, and show how in silico methods, applied to measurements on immature cardiomyocytes, can be used to both identify drug action and to predict its effect in mature cells. Our synthetic and experimental results indicate that optically obtained waveforms of voltage and calcium from microphysiological systems can be inverted into information on drug ion channel blockage, and then, through assuming functional invariance of proteins during maturation, this data can be used to predict drug induced changes in mature ventricular cells. Together, this pipeline of measurements and computational analysis could significantly improve the ability of hiPSC derived cardiomycocytes to predict dangerous drug side effects.

URLhttps://doi.org/10.1038/s41598-018-35858-7
DOI10.1038/s41598-018-35858-7
Citation Key26238