日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Since induced pluripotent stem (iPS) cells have been generated in 2007 from human somatic cells, many studies of disease-specific iPS cells have been reported. Because disease-specific iPS cells can recapitulate disease phenotypes, they are expected to be a novel research tool for in vitro disease modeling to dissect pathogenesis and assist in drug discovery. In terms of cardiovascular diseases, most of the iPS cells have been generated from the patients with inherited arrhythmias or cardiomyopathy. There have been few reports of human iPS cells established from the patients with congenital heart diseases composed of abnormal structures. Most congenital heart diseases are considered to be caused by combinatorial repression of transcription factors and/or impaired epigenetic regulation. Recently, we successfully generated iPS cells from the patients with hypoplastic left heart syndrome (HLHS). We showed that these HLHS-specific iPS cells recapitulated pathogenesis and worked as in vitro disease models for investigating the function of transcription factors during the course of cardiac lineage specification. In this review, we provide an overview of cardiac disease-specific iPS cells and discuss possible uses for dissecting the underlying mechanisms of congenital heart diseases.