Related Experiment Video
Updated: May 11, 2026
Preclinical Cardiac Electrophysiology Assessment by Dual Voltage and Calcium Optical Mapping of Human Organotypic Cardiac Slices
Published on: June 16, 2020
Computational models of ventricular- and atrial-like human induced pluripotent stem cell derived cardiomyocytes
Michelangelo Paci1, Jari Hyttinen, Katriina Aalto-Setälä
1Biomedical Engineering Laboratory-DEI, University of Bologna, Via Venezia 52, 47521, Cesena, FC, Italy.
Insights
Computational models of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) reveal insights into their maturation. These models help understand the electrophysiological differences between hiPSC-CMs and adult myocytes for improved in-vitro drug testing.
Area of Science:
- Cardiology
- Computational Biology
- Stem Cell Research
Background:
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are crucial in-vitro models.
- Phenotypical differences exist between hiPSC-CMs and adult myocytes, necessitating study of hiPSC-CM maturation.
- In-silico investigation complements experimental studies of hiPSC-CMs.
Purpose of the Study:
- To develop computational models of hiPSC-CM action potentials (APs) for ventricular-like and atrial-like phenotypes.
- To quantitatively assess ionic mechanisms contributing to the immature hiPSC-CM phenotype.
- To provide novel computational tools for studying hiPSC-CM electrophysiology.
Main Methods:
- Developed two computational models of hiPSC-CM APs based on experimental data.
- Distinguished between ventricular-like and atrial-like phenotypes during hiPSC-CM differentiation.
- Utilized computational simulations to analyze ionic current roles.
Main Results:
- Successfully reproduced typical hiPSC-CM ventricular-like and atrial-like spontaneous APs.
- Validated models against responses to known current blockers (tetrodotoxin, nifedipine, E4041, 3R4S-Chromanol 293B).
- Simulations indicated immature I Na, I f, and I K1 currents are key to spontaneous beating, while I CaL shifts prolong APs.
Conclusions:
- The study provides two novel computational models for hiPSC-CM electrophysiology.
- These models aid in understanding hiPSC-CM maturation towards adult myocytes.
- The developed tools are valuable for pharmacological studies using hiPSC-CMs.
Abstract:
The clear importance of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) as an in-vitro model highlights the relevance of studying these cells and their function also in-silico. Moreover, the phenotypical differences between the hiPSC-CM and adult myocyte action potentials (APs) call for understanding of how hiPSC-CMs are maturing towards adult myocytes. Using recently published experimental data, we developed two computational models of the hiPSC-CM AP, distinguishing between the ventricular-like and atrial-like phenotypes, emerging during the differentiation process of hiPSC-CMs. Also, we used the computational approach to quantitatively assess the role of ionic mechanisms which are likely responsible for the not completely mature phenotype of hiPSC-CMs. Our models reproduce the typical hiPSC-CM ventricular-like and atrial-like spontaneous APs and the response to prototypical current blockers, namely tetrodotoxine, nifedipine, E4041 and 3R4S-Chromanol 293B. Moreover, simulations using our ventricular-like model suggest that the interplay of immature I Na, I f and I K1 currents has a fundamental role in the hiPSC-CM spontaneous beating whereas a negative shift in I CaL activation causes the observed long lasting AP. In conclusion, this work provides two novel tools useful in investigating the electrophysiological features of hiPSC-CMs, whose importance is growing fast as in-vitro models for pharmacological studies.
More Related Videos
08:06Generation of Ventricular-Like HiPSC-Derived Cardiomyocytes and High-Quality Cell Preparations for Calcium Handling Characterization
Published on: January 17, 2020
09:23Generation, High-Throughput Screening, and Biobanking of Human-Induced Pluripotent Stem Cell-Derived Cardiac Spheroids
Published on: March 10, 2023