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

Abstract：

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Blazeski A,Lowenthal J,Zhu R,Ewoldt J,Boheler KR,Tung L

doi

10.1016/j.stemcr.2019.04.002

subject

Has Abstract

pub_date

2019-05-14 00:00:00

pages

982-995

issue

5

issn

2213-6711

pii

S2213-6711(19)30124-9

journal_volume

12

pub_type

杂志文章

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