Analysis of microRNAs in human iPSC-derived cardiac myocytes
Team: Dena Esfandyari, Deepak Ramanujam, Andrea Welling, Petros Avramopoulos, Urszula Kremser, Bernhard Laggerbauer
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise as “disease in a dish” model to improve our understanding of cardiac disease mechanisms, and also for the development and optimization of therapeutic strategies. Several labs have established hiPSCs-CM from patients suffering from cardiac disorders such as myopathies and channelopathies and, interestingly, the cardiomyocytes derived from these patient-specific iPSCs recapitulate the contractile or electrophysiological features of the disease (Bellin et al., Nat Rev Mol Cell Biol, 2012).
Deregulation of several miRNAs accompanies and contributes to many cardiopathological conditions. Thus, modulation of these molecules may lead to a novel strategy for clinical intervention and a very first step toward translating this approach into clinics could be testing the therapeutic effects of miRNA manipulation in the hiPSC-CMs as the most similar in-vitro model to adult human cardiomyocytes (Kim, G. H., Transl Res, 2013).
Our lab has access to many lines of patient-specific hiPSC, which yield in mature hiPSC-CM. These cells are characterized by advanced optical techniques, such as confocal microscopy and fluorescence resonance energy transfer (FRET), as well as electrophysiological measurement, namely patch clamp and multielectrode array (MEA). We combine these tools with state-of-the art technology for the manipulation of miRNAs, such as AAV vectors for overexpression and LNA-antimiRs for inhibition. Together, these approaches will resolve the role of specific miRNAs in cardiac pathophysiology.
Bellin M. et al. Nat Rev Mol Cell Biol. 2012.
Kim, G. H. Trans Res. 2013.