Engineered Model of Heart Tissue Repair for Exploring Fibrotic Processes and Therapeutic Interventions

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Sep 12

PMID 39266508

Authors

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

Soon will be listed here.

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.

Citing Articles

Advances in cardiac organoid research: implications for cardiovascular disease treatment.

Huang Z, Jia K, Tan Y, Yu Y, Xiao W, Zhou X Cardiovasc Diabetol. 2025; 24(1):25.

PMID: 39827092 PMC: 11743075. DOI: 10.1186/s12933-025-02598-8.

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