Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells

• DOI: 10.1016/j.celrep.2014.09.055
• Publication Date: 2014-10-30T17:01:32Z
• Authors: Faye M. Drawnel; Stefano Boccardo; Michael Prummer; Frédéric Delobel; Alexandra Graff; Michael Weber; Régine Gérard; Laura Badi; Tony Kam-Thong; Lei Bu; Xin Jiang; Jean-Christophe H...; Anna Kiialainen; Elena Jeworutzki; Natsuyo Aoyama; Coby Carlson; Mark Burcin; Gianni Gromo; Markus Boehringer; Henning Stahlberg; Benjamin J. Hall; Maria Chiara Magnone; Kyle Kolaja; Kenneth R. Chien; Jacques Bailly; Roberto Iacone
• Keywords: Diabetic Cardiomyopathy; Clinical phenotype; Phenotypic screening

Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions lifestyle and genetics. We develop environmentally genetically driven in vitro models the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce phenotypic surrogate cardiomyopathy, observing structural functional disarray. Next, consider genetic effects by deriving cardiomyocytes from two patients variable disease progression. The cardiomyopathic phenotype recapitulated patient-specific cells basally, severity dependent on their original status. These are incorporated into successive levels screening platform, identifying drugs that preserve cardiomyocyte during stress. In this work, present induced pluripotent stem cell (iPSC) model complex metabolic condition, showing power technique for discovery testing therapeutic strategies ever-increasing significance.