New robust models for studying atrial fibrillation
September is Atrial Fibrillation Awareness Month! We at Nanion Technologies would like to take this opportunity to emphasize the importance of research on this serious medical condition and to highlight the recent work done by researchers from the University of Göttingen.
Atrial fibrillation is one of the most common types of cardiac arrhythmias. It’s a real concern for millions of people worldwide, as it can lead to blood clots and increases the risk of stroke and heart failure. The progression of atrial fibrillation is particularly challenging; it starts with short episodes and can eventually become a persistent problem that’s resistant to treatment.
One of the significant hurdles in understanding and treating atrial fibrillation has been the lack of accurate human research models. While animal models have provided valuable insights, they don’t fully replicate the intricacies of the human heart. This gap in research tools has made it difficult to develop effective treatments.
In a recent study, researchers from Niels Voigt Lab introduced novel 2D and 3D in vitro models that replicate well the hallmarks of atrial fibrillation and offer a novel platform for human-centric discovery of antiarrhythmic therapies. Essentially, the researchers based their models on two well-known and promising tools: atrial cardiomyocytes derived from human induced pluripotent stem cells (iPSC-aCM) and atrial-engineered human myocardium (aEHM). The challenge was to make these tools simulate atrial fibrillation, to make them exhibit the major characteristics of atrial fibrillation-associated remodeling, such as action potential shortening, reduction of L-type calcium current, or upregulation of the basal inward-rectifier potassium current.
Using an elegant technique of chronic electrical and optical tachypacing via the ultrafast light-gated channelrhodopsin variant f-Chrimson (inserted into iPSCs using CRISPR/Cas9), the researchers were able to reproduce the major hallmarks of atrial fibrillation in both iPSC-aCMs and aEHM, and model the time-dependence of atrial fibrillation-associated remodeling in vitro. The new models displayed changes similar to those observed in atrial fibrillation patients, including alterations in action potentials, L-type calcium currents, potassium currents…
With these models, researchers can now study atrial fibrillation in conditions that more closely resemble the human heart. This not only enhances our understanding of the disease but also paves the way for the development of more effective treatments. Indeed, the study demonstrates that these models can be implemented in high-throughput screening platforms to facilitate human-centric, atrial-specific development of antiarrhythmic therapies. The authors used the high-throughput automated patch-clamp system SyncroPatch 384 to record action potentials as well as L-type calcium, sodium, and inward-rectifier potassium currents in iPSC-aCMs.
In conclusion, while atrial fibrillation remains a challenging condition, advancements like this bring hope. With continued research using these new models, we move a step closer to a future where atrial fibrillation can be better understood and more effectively treated.
You can find the full article here.
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