Engineered Heart Cells Developed To Better Understand Genetic Mechanisms of Atrial Fibrillation

A multidisciplinary team of researchers has developed a more accurate model for understanding the mechanisms underlying atrial fibrillation.

What is Atrial Fibrillation?

Atrial fibrillation (AF) is the most common type of treated heart arrhythmia, a condition where the heart beats too fast or too slowly. Also known as AFib or AF, this condition causes quivering and irregular heartbeats which may lead to blood clots, stroke, and heart failure.

Experts estimate that about 2.7 million to 6.1 million of Americans are suffering from atrial fibrillation. According to the American Heart Association, over 12 million individuals are expected to be diagnosed with atrial fibrillation by the year 2030. In a study conducted in 2013, it was revealed that about 0.5% of the world's population was affected by this disease.

Some people with atrial fibrillation do not show any symptoms. This condition depends on how fast a person's ventricles are beating. If they beat normally or at slightly elevated pace, the patient may not feel anything. However, they may start to notice symptoms if their ventricles beat faster.

Common symptoms of atrial fibrillation include extreme fatigue, irregular heartbeat, and heart palpitations. There could also be a feeling of butterflies or a fish flopping in their chest. In some cases, the patient may experience dizziness, fainting, shortness of breath, and chest pain.

People with atrial fibrillation can be treated with lifestyle changes. There are also antiarrhythmic drugs which work by blocking ion channels in the heart muscle to help regulate heart beat. However, response to treatments may vary among patients, with half of them experiencing recurrent atrial fibrillation shortly after treatment. This is in part due to the lack of understanding of the genetic mechanisms that control the disease.

Understanding AF With Engineered Cells

At the University of Illinois Chicago and Northwestern University, scientists engineered and studied mature atrial cardiomyocytes taken from induced pluripotent stem cells (iSPCs). They aim to address an ongoing challenge in treating atrial fibrillation by generating cells that closely resemble cardiomyocytes from an actual human heart. The results of their findings are presented in the paper "Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation."

Led by Carlos G. Vanoye, the researchers co-cultured the iPSC-derived atrial cardiomyocytes with cardiac fibroblasts. This enabled the cells to acquire characteristics associated with mature atrial cardiomyocytes. Vanoye believes that this system is better at studying various therapeutic approaches against atrial fibrillation.

Vanoye and his colleagues specifically developed a process of arranging proteins within multi-well plates. This enabled them to engineer co-cultures that contain iPSC-atrial myocytes and fibroblasts. The co-cultures enhanced the structural, contractile, electrical, and metabolic maturation of atrial myocytes.

Based on the result of the study, it was found that the co-cultured cells were more mature than cells that are not developed in the presence of fibroblasts. The researchers believe that this approach can help in better understanding cell signaling in the atria, and in testing the efficacy of current and future therapies for atrial fibrillation. Since the co-cultured cells are more mature, they can be more responsive to drugs.

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