Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Autor:	Blazeski A; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA., Lowenthal J; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA., Zhu R; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA., Ewoldt J; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA., Boheler KR; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA; Stem Cell and Regenerative Medicine Consortium, LKS Faculty of Medicine, Hong Kong University, Hong Kong, SAR; Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Tung L; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: ltung@jhu.edu.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2019 May 14; Vol. 12 (5), pp. 982-995. Date of Electronic Publication: 2019 May 02.
DOI:	10.1016/j.stemcr.2019.04.002
Abstrakt:	Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity precludes their use as faithful models of adult myocardium. Here we describe engineered heart slices (EHS), preparations of decellularized porcine myocardium repopulated with hiPSC-CMs that exhibit structural and functional improvements over standard culture. EHS exhibited multicellular, aligned bundles of elongated CMs with organized sarcomeres, positive inotropic responses to isoproterenol, anisotropic conduction of action potentials, and electrophysiological functionality for more than 200 days. We developed a new drug assay, GRIDS, that serves as a "fingerprint" of cardiac drug sensitivity for a range of pacing rates and drug concentrations. GRIDS maps characterized differences in drug sensitivity between EHS and monolayers more clearly than changes in action potential durations or conduction velocities. EHS represent a tissue-like model for long-term culture, structural, and functional improvement, and higher fidelity drug response of hiPSC-CMs. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu