The project aims to develop populations of in silico models of control and disease-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) (i) to investigate their electrophysiological variability and (ii) to integrate and support large scale in vitro drug assays, thus improving and speeding up the current methods for drug development and safety pharmacology tests.
Goal
The human induced pluripotent stem cell (hiPSC) technology enables producing stem cells from patients own cells, to be differentiated into diverse phenotypes, e.g. cardiac cells (hiPSC-CMs). hiPSC-CMs are innovative in vitro models for drug tests since they carry the same patients genetic mutations, showing the same pathological behavior of their natural counterparts. However, hiPSC-CM electrophysiology shows high variability and specific phenotypes cannot be easily obtained in vitro. Also, there is no high-throughput in vitro drug screening method that can provide information on the ionic currents underlying the drug (potentially cardiotoxic) effects.
Mathematical models of the hiPSC-CM electrophysiology enable in silico simulations of the cellular electrophysiology and explain the biophysical mechanisms underlying it. By means of experimentally calibrated populations of in silico hiPSC-CMs we can perform massive simulations of effects of diseases and drugs on hiPSC-CM electrophysiology. Our goals are i) developing tools to study the variability in hiPSC-CMs and ii) using the populations to predict effects and cardiotoxicity of drugs for safety pharmacology research.
Funding source
Academy of Finland
Contact persons
Michelangelo Paci
Principal investigator
michelangelo.paci [at] tut.fi
+358 50 447 9056