ArticleStem cell research & therapy2020
Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- A Beginner's Guide to Cardiac Optical Mapping.Cardiovascular engineering and technology · 2026Review
- Refining the Guinea Pig (Cavia porcellus) Cryo-Injury Model for Cardiac Regeneration and Functional Characterization.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025Article
- Optical mapping of the interface between iPSC-derived grafts and swine myocardium suggests potential arrhythmia mechanisms.NPJ Regenerative medicine · 2025Article
- Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes.Biomolecules · 2024Article
- Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias.Frontiers in cardiovascular medicine · 2024Article
- Graft-host coupling changes can lead to engraftment arrhythmia: a computational study.The Journal of physiology · 2023Article
- Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.Cell stem cell · 2023Article
- Analysis of the effects of bench-scale cell culture platforms and inoculum cell concentrations on PSC aggregate formation and culture.Frontiers in bioengineering and biotechnology · 2023Article
- The effect of sex and age on ex vivo cardiac electrophysiology: insight from a guinea pig model.American journal of physiology. Heart and circulatory physiology · 2023Article
- Computational modeling of aberrant electrical activity following remuscularization with intramyocardially injected pluripotent stem cell-derived cardiomyocytes.Journal of molecular and cellular cardiology · 2022Article
- Carfilzomib Treatment Causes Molecular and Functional Alterations of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Journal of the American Heart Association · 2021Article
- Correction to: Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts.Stem cell research & therapy · 2021Article
- KairoSight: Open-Source Software for the Analysis of Cardiac Optical Data Collected From Multiple Species.Frontiers in physiology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHuman embryonic stem cell-derived cardiomyocytes (hESC-CMs) show tremendous promise for cardiac regeneration, but the successful development of hESC-CM-based therapies requires improved tools to investigate their electrical behavior in recipient hearts. While optical voltage mapping is a powerful technique for studying myocardial electrical activity ex vivo, we have previously shown that intra-cardiac hESC-CM grafts are not labeled by conventional voltage-sensitive fluorescent dyes. We hypothesized that the water-soluble voltage-sensitive dye di-2-ANEPEQ would label engrafted hESC-CMs and thereby facilitate characterization of graft electrical function and integration.
methodsWe developed and validated a novel optical voltage mapping strategy based on the simultaneous imaging of the calcium-sensitive fluorescent protein GCaMP3, a graft-autonomous reporter of graft activation, and optical action potentials (oAPs) derived from di-2-ANEPEQ, which labels both graft and host myocardium. Cardiomyocytes from three different GCaMP3+ hESC lines (H7, RUES2, or ESI-17) were transplanted into guinea pig models of subacute and chronic infarction, followed by optical mapping at 2 weeks post-transplantation.
resultsUse of a water-soluble voltage-sensitive dye revealed pro-arrhythmic properties of GCaMP3+ hESC-CM grafts from all three lines including slow conduction velocity, incomplete host-graft coupling, and spatially heterogeneous patterns of activation that varied beat-to-beat. GCaMP3+ hESC-CMs from the RUES2 and ESI-17 lines both showed prolonged oAP durations both in vitro and in vivo. Although hESC-CMs partially remuscularize the injured hearts, histological evaluation revealed immature graft structure and impaired gap junction expression at this early timepoint.
conclusionSimultaneous imaging of GCaMP3 and di-2-ANEPEQ allowed us to acquire the first unambiguously graft-derived oAPs from hESC-CM-engrafted hearts and yielded critical insights into their arrhythmogenic potential and line-to-line variation.
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