Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions

Pengcheng Yang; Lihang Zhu; Shiya Wang; Jixing Gong; Jonathan Nimal Selvaraj; Lincai Ye; Hanxiao Chen; Yaoyao Zhang; Gongxin Wang; Wanjun Song; Zilong Li; Lin Cai; Hao Zhang; Donghui Zhang

doi:10.1038/s41467-024-52221-9

Nature Communications (Sep 2024)

Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions

Pengcheng Yang,
Lihang Zhu,
Shiya Wang,
Jixing Gong,
Jonathan Nimal Selvaraj,
Lincai Ye,
Hanxiao Chen,
Yaoyao Zhang,
Gongxin Wang,
Wanjun Song,
Zilong Li,
Lin Cai,
Hao Zhang,
Donghui Zhang

Affiliations

Pengcheng Yang: State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University
Lihang Zhu: Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University
Shiya Wang: State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University
Jixing Gong: Center of Translational Medicine, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat‐Sen University
Jonathan Nimal Selvaraj: State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University
Lincai Ye: Shanghai Institute for Congenital Heart Diseases, Shanghai Children’s Medical Center, National Children’s Medical Center
Hanxiao Chen: Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University
Yaoyao Zhang: Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University
Gongxin Wang: Henan SCOPE Research Institute of Electrophysiology Co. Ltd.
Wanjun Song: Beijing Geek Gene Technology Co. Ltd.
Zilong Li: State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University
Lin Cai: State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University
Hao Zhang: Shanghai Institute for Congenital Heart Diseases, Shanghai Children’s Medical Center, National Children’s Medical Center
Donghui Zhang: State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University

DOI: https://doi.org/10.1038/s41467-024-52221-9
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 21

Abstract

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Abstract Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFβ inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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