2. Academic Validation
  3. Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions

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

  • Nat Commun. 2024 Sep 12;15(1):7996. doi: 10.1038/s41467-024-52221-9.
Pengcheng Yang # 1,  Lihang Zhu # 2,  Shiya Wang 1,  Jixing Gong 3,  Jonathan Nimal Selvaraj 1,  Lincai Ye 4,  Hanxiao Chen 5,  Yaoyao Zhang 5,  Gongxin Wang 6,  Wanjun Song 7,  Zilong Li 1,  Lin Cai 8,  Hao Zhang 9,  Donghui Zhang 10 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
  • 2 Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • 3 Center of Translational Medicine, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, China.
  • 4 Shanghai Institute for Congenital Heart Diseases, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai, China.
  • 5 Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  • 6 Henan SCOPE Research Institute of Electrophysiology Co. Ltd., Kaifeng, China.
  • 7 Beijing Geek Gene Technology Co. Ltd., Beijing, China.
  • 8 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China. cailin12@hubu.edu.cn.
  • 9 Shanghai Institute for Congenital Heart Diseases, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai, China. Drzhanghao@yahoo.com.
  • 10 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China. Dongh.zhang@hubu.edu.cn.
  • 11 Cardiovascular Research Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Dongh.zhang@hubu.edu.cn.
  • # Contributed equally.
PMID: 39266508 DOI: 10.1038/s41467-024-52221-9
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.

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