These findings suggest that our cardiomyocyte cell lines recapitulate the pathology of arrhythmogenic cardiomyopathy and provide a rapid and convenient platform for developing gene-based therapies for this disease
Shuichiro Higo
To investigate how cells derived from patients behave in the laboratory, the researchers first took a blood sample from a young patient with arrhythmogenic cardiomyopathy, induced some of the blood cells to become stem cells, and then differentiated these stem cells into heart cells. They then modified this original batch of heart cells into three different cell lines with precisely adjusted PKP2 expression based on how many mutated or intact copies of the gene were present. “The cells with two mutated copies of PKP2 clearly exhibited reduced contractility and impaired desmosome assembly due to plakophilin-2 deficiency,” explains senior author Shuichiro Higo. “These effects were also observed in cells with only one mutated copy of PKP2, although they were less severe.”
Replacing the mutated PKP2 with an intact copy of the gene repaired the defects in both cell contraction and desmosome assembly, which the researchers were able to observe using a time-lapse approach and fluorescently labeled desmosomes. “These findings suggest that our cardiomyocyte cell lines recapitulate the pathology of arrhythmogenic cardiomyopathy and provide a rapid and convenient platform for developing gene-based therapies for this disease,” says Higo.
Given that PKP2 is the most common gene associated with arrhythmogenic cardiomyopathy, and that PKP2 mutations can lead to severe disease, new therapeutic approaches could help halt disease progression. The findings from this study suggest that gene replacement therapy could be a valuable way of treating patients with this condition and the cell lines created in this study are a viable model to test new therapies for arrhythmogenic cardiomyopathy on.
Source: Osaka University
Source: Healthcare in Europe
