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

Drawnel, Faye M. and Boccardo, Stefano and Prummer, Michael and Delobel, Frédéric and Graff, Alexandra and Weber, Michael and Gérard, Régine and Badi, Laura and Kam-Thong, Tony and Bu, Lei and Jiang, Xin and Hoflack, Jean-Christophe and Kiialainen, Anna and Jeworutzki, Elena and Aoyama, Natsuyo and Carlson, Coby and Burcin, Mark and Gromo, Gianni and Boehringer, Markus and Stahlberg, Henning and Hall, Benjamin J. and Magnone, Maria Chiara and Kolaja, Kyle and Chien, Kenneth R. and Bailly, Jacques and Iacone, Roberto. (2014) Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells. Cell reports, Vol. 9, H. 3. pp. 810-820.

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Official URL: http://edoc.unibas.ch/dok/A6329109

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Abstract

Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:2211-1247
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:58
Deposited On:06 Feb 2015 09:58

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