Three-dimensional filamentous human diseased cardiac tissue model

Zhen Ma; Sangmo Koo; Micaela A Finnegan; Peter Loskill; Nathaniel Huebsch; Natalie C Marks; Bruce R Conklin; Costas P Grigoropoulos; Kevin E Healy

doi:10.1016/j.biomaterials.2013.10.052

Three-dimensional filamentous human diseased cardiac tissue model

Biomaterials. 2014 Feb;35(5):1367-77. doi: 10.1016/j.biomaterials.2013.10.052. Epub 2013 Nov 21.

Authors

Zhen Ma¹, Sangmo Koo², Micaela A Finnegan¹, Peter Loskill¹, Nathaniel Huebsch³, Natalie C Marks¹, Bruce R Conklin³, Costas P Grigoropoulos², Kevin E Healy⁴

Affiliations

¹ Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
² Department of Mechanical Engineering, University of California, Berkeley, CA 94720, USA.
³ 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.
⁴ 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.

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.

Keywords: Cardiac contractility; Cardiac disease model; Drug testing; Induced pluripotent stem cells; Long QT syndrome; Two-photon initiated polymerization.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Case-Control Studies
Cell Differentiation
Drug Evaluation, Preclinical
Flow Cytometry
Humans
Induced Pluripotent Stem Cells / pathology
Long QT Syndrome / drug therapy
Long QT Syndrome / pathology*
Microscopy, Atomic Force
Microscopy, Electron, Scanning
Models, Biological*
Real-Time Polymerase Chain Reaction

Abstract

Publication types

MeSH terms

Grants and funding