Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues

Jaimeson Veldhuizen; Helen F. Mann; Nina Karamanova; Wade D. Van Horn; Raymond Q. Migrino; David A. Brafman; Mehdi Nikkhah

doi:10.1126/sciadv.abq6720

December 16, 2022Science AdvancesOpen Access

Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues

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Key Points

To model long QT syndrome type 2 pathophysiology in vitro and evaluate pharmacological rescue using gene-edited human induced pluripotent stem cell-derived cardiomyocytes in a 3D tissue-on-a-chip platform.
Engineered 3D cardiac tissue-on-a-chip models using gene-edited hiPSC-derived cardiomyocytes harboring the R531W mutation.
Characterized functional properties of the tissues by assessing calcium handling and responses to β-agonist stimulation.
Tested pharmacological interventions to investigate phenotypic rescue of LQTS2 on the chip platform.
Revealed a potential pathological mechanism driven by the R531W mutation in 3D LQTS2 cardiac tissues.
Demonstrated functional disease hallmarks through altered calcium handling and aberrant responses to β-agonist stimulation.
Achieved phenotypic rescue of LQTS2 features using targeted pharmacological intervention on the chip model.

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Implication

Demonstrates a 3D tissue-on-a-chip model of long QT syndrome type 2 using gene-edited cardiac cells, suggesting a platform for testing pharmacological rescue strategies.

Abstract

-edited hiPSC-CMs, revealing a possible mechanism of R531W mutation in LQTS2 pathophysiology. Following creation of a 3D LQTS2 tissue-on-a-chip, the tissues were extensively characterized, through analysis of calcium handling and response to β-agonist. Furthermore, attempted phenotypic rescue via pharmacological intervention of LQTS2 on a chip was investigated.

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Veldhuizen et al. (2022) studied this question.

synapsesocial.com/papers/69f2cb39be8e9f1f31c5784d https://doi.org/10.1126/sciadv.abq6720

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Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues

Key Points

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Implication

Abstract

Discussion

Cite This Study

Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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