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用于探索纤维化过程和治疗干预的心脏组织修复工程模型。

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

机构信息

State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.

Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.

出版信息

Nat Commun. 2024 Sep 12;15(1):7996. doi: 10.1038/s41467-024-52221-9.

DOI:10.1038/s41467-024-52221-9
PMID:39266508
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11393355/
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.

摘要

人工心脏组织的进步增强了我们对心脏细胞变化的理解。然而，模拟心肌梗死后病理性重构的人类模型对于治疗开发仍然至关重要。在这里，我们开发了一种心肌修复的工程模型，可复制包括缺氧应激、纤维化和电生理功能障碍在内的阶段性重塑过程。转录组分析确定了与细胞命运转变相关的九个关键信号通路，从而评估了十七种调节剂在小型修复模型中的治疗潜力。评分系统定量评估了异常电生理的恢复情况，表明 TGFβ 抑制剂 SB431542、Rho 激酶抑制剂 Y27632 和 WNT 激活剂 CHIR99021 的阶段性组合治疗比单一因素治疗在工程化和小鼠心肌梗死模型中均能更有效地恢复功能。这种工程心脏组织修复模型有效地捕获了心肌梗死后的阶段性重塑，为发现缺血性心脏病的治疗靶点提供了一个关键平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/0ad15b22b7d9/41467_2024_52221_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/28ed2e4f4bb5/41467_2024_52221_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/97cde2798325/41467_2024_52221_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/559d25022fbc/41467_2024_52221_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/bfc04f0fb349/41467_2024_52221_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/fa4d712edb0f/41467_2024_52221_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/5482531cdf6e/41467_2024_52221_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/7de80098ebd2/41467_2024_52221_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/0ad15b22b7d9/41467_2024_52221_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/28ed2e4f4bb5/41467_2024_52221_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/97cde2798325/41467_2024_52221_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/559d25022fbc/41467_2024_52221_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/bfc04f0fb349/41467_2024_52221_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/fa4d712edb0f/41467_2024_52221_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/5482531cdf6e/41467_2024_52221_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/7de80098ebd2/41467_2024_52221_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1c/11393355/0ad15b22b7d9/41467_2024_52221_Fig8_HTML.jpg

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本文引用的文献

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Nat Cardiovasc Res. 2022 Apr;1(4):312-321. doi: 10.1038/s44161-022-00043-7. Epub 2022 Apr 13.
2
Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development.转录因子 NFYa 在小鼠胎儿心脏发育过程中控制心肌细胞代谢和增殖。
Dev Cell. 2023 Dec 18;58(24):2867-2880.e7. doi: 10.1016/j.devcel.2023.10.012. Epub 2023 Nov 15.
3
A transient wave of Bhlhe41 resident macrophages enables remodeling of the developing infarcted myocardium.
细胞外基质硬度：针对成纤维细胞炎症的生物医学应用中机械转导与机械生物学响应驱动策略
Polymers (Basel). 2025 Mar 20;17(6):822. doi: 10.3390/polym17060822.
4
Advances in cardiac organoid research: implications for cardiovascular disease treatment.心脏类器官研究进展：对心血管疾病治疗的意义
Cardiovasc Diabetol. 2025 Jan 18;24(1):25. doi: 10.1186/s12933-025-02598-8.
一过性 Bhlhe41 驻留巨噬细胞波可重塑发育中梗死的心肌。
Cell Rep. 2023 Oct 31;42(10):113174. doi: 10.1016/j.celrep.2023.113174. Epub 2023 Sep 25.
4
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Sci Rep. 2023 Jul 26;13(1):12137. doi: 10.1038/s41598-023-39369-y.
5
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