title: Three-dimensional filamentous human diseased cardiac tissue model.
abstract: A human in vitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an in vitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity.
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Mechanical Engineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Sangmo
authors.initials: S
authors.lastname: Koo
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Micaela A
authors.initials: MA
authors.lastname: Finnegan
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Loskill
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Huebsch
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Marks
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Conklin
authors.affiliation: Department of Mechanical Engineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Costas P
authors.initials: CP
authors.lastname: Grigoropoulos
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Material Science and Engineering, University of California, Berkeley, CA 94720, USA. Electronic address: kehealy@berkeley.edu.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Healy
mesh_terms: D016022:Case-Control Studies; D002454:Cell Differentiation; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology; D008133:Long QT Syndrome / Q000188:drug therapy / Q000473:pathology*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D060888:Real-Time Polymerase Chain Reaction
keywords: Cardiac contractility; Cardiac disease model; Drug testing; Induced pluripotent stem cells; Long QT syndrome; Two-photon initiated polymerization