Researchers have engineered stem cells that do not generate dangerous arrhythmias, a complication that has until now thwarted efforts to develop stem cell therapies for injured hearts. Researchers suspected that transplanted stem cells that did not generate arrhythmias were behaving like early embryonic cells chaotically generating signals and causing dangerous heart rhythms. So the researchers used a technique called RNA sequencing to find out which ion channels were being made at different times during cell maturation. Next, the scientists used CRISPR-based genome editing to systematically eliminate depolarizing genes or turn on repolarizing genes, but none of the single-gene edits eliminated the fast heart rhythms. The researchers then undertook a painstaking process of “playing the combinations” by making double and triple gene modifications. Unfortunately, none of these modifications eliminated the arrhythmia. Finally, the scientists created a stem cell line in which three depolarizing genes were eliminated and one repolarizing gene was activated. The generated heart muscle cells were electrically resting, like adult heart muscle, but they contracted when they received an electrical signal to mimic a natural pacemaker. The researchers named these cells “MEDUSA.”
