Electrical stimulation of human heart muscle cells engineered from human stem cells aids their development and function, reports a paper published this week in Nature Communications. The authors propose that these results in cells, if confirmed in animal models, could aid current developments in stem cell therapy that seek to treat diseases affecting the human heart.
The structural and functional immaturity of heart muscle cells (cardiomyocytes) that are derived from stem-cells has so far hampered their therapeutic potential to be implanted in the heart and replace damaged heart tissue. In fact, engineered cardiomyocytes typically generate too few connexins - proteins that allow narrow gaps between adjacent heart muscle cells to be formed - to allow ions and small molecules to move freely in the heart. As a consequence, the immature cardiomyocytes do not connect properly to the host myocardium, the muscular wall of the heart, when implanted. In addition, immature cardiomyocytes may generate abnormal, spontaneous electrical impulses, leading to irregular beating of the heart (arrhythmia), which can be life-threatening.
Gordana Vunjak-Novakovic and colleagues grow human, stem cell-derived cardiomyocytes and engineer them into three-dimensional structures. They then expose these structures to continuous electrical signals - which mimic those of the healthy heart in strength - over a period of one week. They show that this electrical stimulation increases cardiomyocyte connectivity and the regularity of muscle contraction. The immature cardiomyocites respond to the electrical signals by making more connexins, which allows for rapid electrical conduction between cells, and by generating more so-called hERG protein - a building block of potassium channels, which regulate normal electrical activity in the heart.
These findings, although preliminary and yet to be tested in animal models, suggest that electrical stimulation of immature cardiomyocytes may be used to drive their development to a stage that will secure their complete integration and beating synchronization with a host heart muscle.