Engineered stem cells do not provoke dangerous heart rhythms, a challenge that has prevented the progress of stem cell transplants for damaged hearts. Researchers at the University of Washington School of Medicine in Seattle have successfully created stem cells that do not cause dangerous arrhythmi
Researchers at the University of Washington School of Medicine have successfully engineered stem cells that do not cause dangerous arrhythmias, a major complication previously hindering stem-cell therapies for injured hearts. By using CRISPR-based genome editing to modify ion channels in the stem cells, the team created a new line of cells called “MEDUSA,” which engraft in the heart, mature, and integrate into heart muscle without generating dangerous heart rates.
To create their therapeutic heart cells, the Seattle researchers used pluripotent stem cells. Unlike adult stem cells, which have specialized to become specific cell types, pluripotent stem cells can become any type of cell in the body. But there was one major complication. During the early weeks of engraftment, the hearts tended to beat at a dangerously high rate. Unless a way could be found to prevent or suppress this problem, stem cells could not become a safe treatment for myocardial infarction and heart failure.
In pacemaker cells, the voltage cycles back and forth from negative to positive . Murry compares it to a metronome with positive ions swooshing in and out of the cell through these channels. The rate at which this cycle of repolarization and depolarization occurs determines the heart rate. To determine which ion channels were the culprits carrying the arrhythmia-causing current, the scientists used CRISPR-based genome editing to systematically knock out depolarizing genes or to activate repolarizing genes. This proved surprisingly complex. They had hypothesized that there would be a single ion channel causing the arrhythmia, but none of the single-gene edits eliminated the rapid heart rhythms.
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