title: High throughput physiological screening of iPSC-derived cardiomyocytes for drug development.
abstract: Cardiac drug discovery is hampered by the reliance on non-human animal and cellular models with inadequate throughput and physiological fidelity to accurately identify new targets and test novel therapeutic strategies. Similarly, adverse drug effects on the heart are challenging to model, contributing to costly failure of drugs during development and even after market launch. Human induced pluripotent stem cell derived cardiac tissue represents a potentially powerful means to model aspects of heart physiology relevant to disease and adverse drug effects, providing both the human context and throughput needed to improve the efficiency of drug development. Here we review emerging technologies for high throughput measurements of cardiomyocyte physiology, and comment on the promises and challenges of using iPSC-derived cardiomyocytes to model disease and introduce the human context into early stages of drug discovery. This article is part of a Special Issue entitled: Cardiomyocyte biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California, San Diego, 9500 Gilman Drive MC 0411, La Jolla, CA 92093-0411, USA.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Del Álamo
authors.affiliation: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093-0412, USA; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, CA 92037, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Lemons
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California, San Diego, 9500 Gilman Drive MC 0411, La Jolla, CA 92093-0411, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Serrano
authors.affiliation: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093-0412, USA; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, CA 92037, USA; Stanford Cardiovascular Institute, 265 Campus Dr., Stanford, CA 94305-5454, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Savchenko
authors.affiliation: ACEA Biosciences, Inc., 6779 Mesa Ridge Road, San Diego, CA 92121, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cerignoli
authors.affiliation: Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, CA 92037, USA.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
authors.affiliation: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093-0412, USA; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, CA 92037, USA; Stanford Cardiovascular Institute, 265 Campus Dr., Stanford, CA 94305-5454, USA. Electronic address: mmercola@stanford.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Mercola
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D055808:Drug Discovery / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D057166:High-Throughput Screening Assays; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D018570:Risk Assessment
chemical_list: D002317:Cardiovascular Agents
keywords: Automated microscopy; Cardiomyocyte; Drug discovery; Heart; High content screening; Particle image velocimetry; Physiology