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Pssc Research Paper

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Precision Medicine and Generation of Human Cardiomyocytes from iPSCs
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Advances in Application of iPSC-derived Cardiomyocytes for Future Medicine
-Modeling Inherited cardiomyopathy with human iPSC-derived cardiomyocytes
The advent of iPS cell technology and improvements in protocols for cardiomyocytes differentiation open the door to using iPSC-CMs platform for disease modeling and toxicological assays in various cardiovascular diseases. To data, one of the most successful area in research application of iPSC-CMs is the development of the disease model of inherited cardiovascular disease.

For example, hypertrophic cardiomyopathy (HCM), which is a common genetic cardiomyopathy characterized by marked hypertrophy of …show more content…

More recently, we have shown the usefulness of the iPSC-CM technology to understand molecular mechanism in cardiac developmental defects. Left ventricular non-compaction (LVNC) is a relatively common form of cardiomyopathy in children, and is typically characterized by prominent trabeculations with deep recesses. We generated iPSC-CMs from LVNC patients carrying a stop-gain mutation in the TBX20 gene (Try317*), and demonstrated that LVNC-iPSC-CMs recapitulate the proliferative defects associated with the disease. We found that TGF-β signaling pathway is abnormally activated due to functional disturbance of TBX20 in LVNC-iPSC-CMs, and inhibition of TGF-β signaling or TBX20 mutation correction by transcription activator-like receptor nuclease (TALEN) rescued the proliferative defect in LVNC-iPSC-CMs.

Recent advances in genome-editing tools, such as TALEN and CRISPR (clustered regularly interspaced short palindromic repeat), have father expand the potential application of iPSC-CM technology for precision medicine. Currently, disease diagnosis and prognosis in asymptomatic individuals carrying a potential disease-causing mutation mainly rely on careful monitoring of biomarkers or heart function, and their family history. However, this approach sometimes requires long-term medical follow-up, leading a

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