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Updated: Jun 14, 2025
Model of Ischemic Heart Disease and Video-Based Comparison of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytes
Published on: May 5, 2020
Characteristics and pharmacological responsiveness in hiPSC models of inherited cardiomyopathy
Merel Gerritse1, Willem B van Ham2, Chris Denning3
1Utrecht Regenerative Medicine Center, Circulatory Health Research Center, University Utrecht, 3584 CS Utrecht, the Netherlands; Department of Medical Physiology, Division Heart & Lungs, University Medical Center Utrecht, 3584 CM Utrecht, the Netherlands.
Insights
Inherited cardiomyopathies, a leading cause of heart failure, share common cellular defects despite diverse genetic origins. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) reveal these shared phenotypes and potential therapeutic strategies.
Area of Science:
- Cardiology
- Genetics
- Stem Cell Biology
Background:
- Inherited cardiomyopathies are a significant cause of heart failure with diverse genetic underpinnings.
- Overlapping phenotypic defects are observed in patients with different genetic variants, complicating disease understanding and treatment.
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a robust model for studying these complex genetic heart conditions.
Purpose of the Study:
- To systematically review and summarize morphological and functional phenotypes of inherited cardiomyopathies using hiPSC-CM models.
- To evaluate and score the effectiveness of therapeutic strategies applied to cardiomyopathic hiPSC-CMs.
- To identify common disease mechanisms and therapeutic prospects for improved clinical translation.
Main Methods:
- A comprehensive review of 90 studies focusing on 24 cardiomyopathy-associated genes.
- Systematic summarization of morphological and functional phenotypes in hiPSC-CMs derived from patients or engineered with patient variants.
- Compilation and effectiveness scoring of therapeutic interventions tested in hiPSC-CM models.
Main Results:
- Identification of multiple overlapping phenotypic defects across different genetic variants in hiPSC-CMs.
- Discovery of specific cellular characteristics associated with particular genetic variants.
- Compilation of data on therapeutic strategies and their efficacy in hiPSC-CM models.
Conclusions:
- Shared pathogenic mechanisms and phenotypes exist in inherited cardiomyopathies, offering opportunities for targeted therapies.
- hiPSC-CMs are valuable tools for dissecting disease mechanisms and evaluating potential treatments for genetic heart conditions.
- Further research focusing on hiPSC-CM findings can accelerate clinical translation for inherited cardiomyopathies.
Abstract:
Inherited cardiomyopathies are a major cause of heart failure in all age groups, often with an onset in adolescence or early adult life. More than a thousand variants in approximately one hundred genes are associated with cardiomyopathies. Interestingly, many genetic cardiomyopathies display overlapping phenotypical defects in patients, despite the diversity of the initial pathogenic variants. Understanding how the underlying pathophysiology of genetic cardiomyopathies leads to these phenotypes will improve insights into a patient's disease course, and creates the opportunity for conceiving treatment strategies. Moreover, therapeutic strategies can be used to treat multiple cardiomyopathies based on shared phenotypes. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer reliable, high-throughput models for studying molecular and cellular characteristics of hereditary cardiomyopathies. hiPSC-CMs are produced relatively easily, either by directly originating them from patients, or by introducing patient-specific genetic variants in healthy lines. This review evaluates 90 studies on 24 cardiomyopathy-associated genes and systematically summarises the morphological and functional phenotypes observed in hiPSC-CMs. Additionally, treatment strategies applied in cardiomyopathic hiPSC-CMs are compiled and scored for effectiveness. Multiple overlapping phenotypic defects were identified in cardiomyocytes with different variants, whereas certain characteristics were only associated with specific genetic variants. Based on these findings, common mechanisms, therapeutic prospects, and considerations for future research are discussed with the aim to improve clinical translation from hiPSC-CMs to patients.
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