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CRISPR engineering cardiometabolic disease models using human iPSC

iPSC and Stem Cell Lab, Edward Via College of Osteopathic Medicine and Gibbs Research Institute, Spartanburg, SC 29303

Special Issue: iPS Cell Technologies in Human Diseases

Since their introduction, human induced pluripotent stem cells (iPSCs) have enhanced the ways human disease processes are evaluated. Only eleven years ago, Yamanaka and colleagues showed somatic cells could be reprogrammed to induced pluripotent cells (iPSC) employing four transcription factors. Since that initial demonstration, much progress has been made in establishing human cardiac cell models that recapitulate diseases using easily obtained patient somatic cells such as fibroblasts or peripheral blood cells. Investigators now have access, through established small molecule methods to differentiate iPSCs to cardiomyocytes, hepatocytes, neurons, astrocytes and many other cell types of interest. This capability provides valuable cell models of human disease derived from patient cells or CRISPR gene-edited cells that introduce or repair patient disease mutations. In many cases, these manipulations create unique cell models and address the need for scalability and reproducibility of cell samples. Consequently, human iPSC derived cells can be used to query cellular and pathological mechanisms potentially providing bio-information that animal models may be unable to report. In this article, we review iPSC derived cardiomyocyte models of cardiometabolic disease and demonstrate the power of these technologies to probe gene function for biological and clinical significance and to capture pathological signatures from genetic variation in human cardiac disease. Examples of the iPSC derived cardiometabolic disease models including channelopathies, metabolic disease and cardiomyopathy are presented.
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