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人脐带间充质干细胞外泌体-EGR1微针贴片通过调节氧化应激和线粒体自噬对心肌梗死/再灌注损伤的心脏保护作用

Cardioprotective effects of hUCMSCs-Exosi-EGR1 MN patch in MI/RI by modulating oxidative stress and mitophagy.

作者信息

Huang Chen, Zhang Xun, Wu Shi-Xiong, Chang Qing, Zheng Zhi-Kun, Xu Jing

机构信息

Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.

出版信息

Mater Today Bio. 2025 Jan 19;31:101500. doi: 10.1016/j.mtbio.2025.101500. eCollection 2025 Apr.

DOI:10.1016/j.mtbio.2025.101500
PMID:39944530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11815289/
Abstract

In an effort to address the detrimental effects of myocardial ischemia/reperfusion injury (MI/RI), this study introduces a novel therapeutic strategy that involves a microneedle (MN) patch loaded with exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) and carrying small interfering RNA (siRNA) targeting early growth response-1 (EGR1). By delivering hUCMSCs-derived exosomes containing EGR1 siRNA (hUCMSCs-Exosi-EGR1), the MN patch demonstrated promising cardioprotective effects in both and models of MI/RI. The results highlighted the efficacy of Exosi-EGR1 in enhancing cardiomyocyte viability, attenuating oxidative stress levels, and fostering mitophagy regulation. Moreover, the Exosi-EGR1 MN patch exhibited excellent mechanical properties and sustained drug release characteristics when embedded in a Gelatin methacryloyl (GelMA) matrix. Noteworthy outcomes from experiments included significant improvements in cardiac function, reduced cardiac fibrosis, and decreased apoptosis rates in MI/RI mice, emphasizing the potential therapeutic value of the Exosi-EGR1 MN patch in mitigating MI/RI through modulation of oxidative stress and mitophagy mechanisms.

摘要

为了应对心肌缺血/再灌注损伤（MI/RI）的有害影响，本研究引入了一种新的治疗策略，即使用一种微针（MN）贴片，该贴片负载有人脐带间充质干细胞（hUCMSCs）来源的外泌体，并携带靶向早期生长反应-1（EGR1）的小干扰RNA（siRNA）。通过递送含有EGR1 siRNA的hUCMSCs来源的外泌体（hUCMSCs-Exosi-EGR1），MN贴片在MI/RI的体内和体外模型中均显示出有前景的心脏保护作用。结果突出了Exosi-EGR1在提高心肌细胞活力、减轻氧化应激水平和促进线粒体自噬调节方面的功效。此外，当嵌入甲基丙烯酸明胶（GelMA）基质中时，Exosi-EGR1 MN贴片表现出优异的机械性能和持续的药物释放特性。体内实验的显著结果包括MI/RI小鼠的心脏功能显著改善、心脏纤维化减轻和凋亡率降低，强调了Exosi-EGR1 MN贴片通过调节氧化应激和线粒体自噬机制减轻MI/RI的潜在治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/d99dc5579e40/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/0240674d85b8/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/a18e028cdebe/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/706c213f2653/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/be99538c6527/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/453b4123787c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/116aed5d966c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/e88beb37ddfa/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/2a4d093b3c92/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/fb4d57e93806/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/2a3dcf39ed52/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/e87064836ecc/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/d99dc5579e40/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/0240674d85b8/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/a18e028cdebe/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/706c213f2653/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/be99538c6527/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/453b4123787c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/116aed5d966c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/e88beb37ddfa/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/2a4d093b3c92/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/fb4d57e93806/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/2a3dcf39ed52/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/e87064836ecc/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d3/11815289/d99dc5579e40/mmcfigs3.jpg

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引用本文的文献

[1]
Bioengineered microneedles and nanomedicine as therapeutic platform for tissue regeneration.

J Nanobiotechnology. 2025-8-19

本文引用的文献

[1]
Nanoparticle-Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia-Reperfusion Injury.

ACS Nano. 2024-7-17

[2]
miR-124-3p downregulates EGR1 to suppress ischemia-hypoxia reperfusion injury in human iPS cell-derived cardiomyocytes.

Sci Rep. 2024-6-27

[3]
Layer-by-layer microneedle patch with antibacterial and antioxidant dual activities for accelerating bacterial-infected wound healing.

Colloids Surf B Biointerfaces. 2023-11

[4]
Macrophages in the Inflammatory Phase following Myocardial Infarction: Role of Exogenous Ubiquitin.

Biology (Basel). 2023-9-20

[5]
hUC-MSC-EV-miR-24 enhances the protective effect of dexmedetomidine preconditioning against myocardial ischemia-reperfusion injury through the KEAP1/Nrf2/HO-1 signaling.

Drug Deliv Transl Res. 2024-1

[6]
Lyophilization Based Isolation of Exosomes.

Int J Mol Sci. 2023-6-22

[7]
Extracellular lncRNAs secreted and absorbed by cardiomyocytes.

J Cell Biochem. 2023-6

[8]
Early growth response-1: Key mediators of cell death and novel targets for cardiovascular disease therapy.

Front Cardiovasc Med. 2023-3-28

[9]
Plasma exosome miRNA-26b-3p derived from idiopathic short stature impairs longitudinal bone growth via the AKAP2/ERK1/2 axis.

J Nanobiotechnology. 2023-3-16

[10]
Microneedle Patch Loaded with Exosomes Containing MicroRNA-29b Prevents Cardiac Fibrosis after Myocardial Infarction.

Adv Healthc Mater. 2023-5

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