Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation
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Published on: June 16, 2020
Pim R R van Gorp1, Serge A Trines1, Daniël A Pijnappels1
1Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands.
Insights
This review explores in vitro atrial cell models for studying atrial fibrillation (AF) mechanisms. These models offer standardized approaches to understand AF
Area of Science:
- Cardiology
- Biomedical Engineering
- Cell Biology
Background:
- Atrial fibrillation (AF) is a prevalent cardiac arrhythmia with significant health and economic burdens.
- Current treatments for AF, including antiarrhythmic drugs and invasive procedures, have limitations in efficacy and safety.
- Understanding AF's complex pathophysiology, involving tissue remodeling, is crucial for developing novel therapies.
Purpose of the Study:
- To review current two- and three-dimensional multicellular in vitro systems for studying atrial arrhythmias.
- To evaluate the utility of various atrial cell culture models in investigating AF mechanisms.
- To discuss the strengths and weaknesses of different in vitro models for future AF research.
Main Methods:
- Review of existing literature on in vitro models for atrial arrhythmia research.
- Categorization of models including primary atrial cardiomyocytes, stem cell-derived CMs, and immortalized CMs.
- Analysis of the suitability of these models for studying AF initiation, maintenance, and termination.
Main Results:
- Monolayers of atrial cells provide a controllable in vitro system to study arrhythmia mechanisms.
- Various cell culture models, including primary, stem cell-derived, and immortalized cardiomyocytes, are available.
- Each model system possesses unique advantages and disadvantages for investigating atrial arrhythmias.
Conclusions:
- In vitro atrial cell models are valuable tools for dissecting the complex mechanisms of atrial arrhythmias.
- The choice of model system depends on the specific research question regarding AF pathophysiology.
- Further development and application of these models are essential for advancing AF treatment strategies.
Abstract:
Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a large socioeconomic impact due to its associated morbidity, mortality, reduction in quality of life and health care costs. Currently, antiarrhythmic drug therapy is the first line of treatment for most symptomatic AF patients, despite its limited efficacy, the risk of inducing potentially life-threating ventricular tachyarrhythmias as well as other side effects. Alternative, in-hospital treatment modalities consisting of electrical cardioversion and invasive catheter ablation improve patients' symptoms, but often have to be repeated and are still associated with serious complications and only suitable for specific subgroups of AF patients. The development and progression of AF generally results from the interplay of multiple disease pathways and is accompanied by structural and functional (e.g., electrical) tissue remodeling. Rational development of novel treatment modalities for AF, with its many different etiologies, requires a comprehensive insight into the complex pathophysiological mechanisms. Monolayers of atrial cells represent a simplified surrogate of atrial tissue well-suited to investigate atrial arrhythmia mechanisms, since they can easily be used in a standardized, systematic and controllable manner to study the role of specific pathways and processes in the genesis, perpetuation and termination of atrial arrhythmias. In this review, we provide an overview of the currently available two- and three-dimensional multicellular in vitro systems for investigating the initiation, maintenance and termination of atrial arrhythmias and AF. This encompasses cultures of primary (animal-derived) atrial cardiomyocytes (CMs), pluripotent stem cell-derived atrial-like CMs and (conditionally) immortalized atrial CMs. The strengths and weaknesses of each of these model systems for studying atrial arrhythmias will be discussed as well as their implications for future studies.
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