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外泌体对心律失常的治疗潜力:临床前证据的系统评价

Therapeutic Potential of Exosome for Cardiac Arrhythmia: A Systematic Review of Preclinical Evidence.

作者信息

Harsoyo Agus, Eri Rifqi Rizkani, Zahrani Sania, Balweel Haikal, Tafriend Novaro Adeneur

机构信息

Department of Cardiology, Gatot Soebroto Army Central Hospital, Jakarta, Indonesia.

Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

出版信息

Stem Cell Rev Rep. 2025 Oct;21(7):2066-2088. doi: 10.1007/s12015-025-10952-2. Epub 2025 Jul 29.

DOI:10.1007/s12015-025-10952-2
PMID:40728810
Abstract

INTRODUCTION

Cardiac arrhythmias remain a major global health concern despite advances in therapeutic strategies. In certain clinical contexts, novel and minimally invasive therapies are particularly desirable. Exosomes have emerged as a promising approach for various diseases, but their therapeutic role in arrhythmias remains underexplored. This systematic review aims to synthesize and evaluate current evidence on the potential of exosome-based therapy for cardiac arrhythmias.

METHODS

A comprehensive literature search was conducted in PubMed, ScienceDirect, and SCOPUS in accordance with PRISMA guidelines, using the search terms: (exosome) AND ((cardiac conduction) OR (arrhythmia)). Studies were included if they investigated the acute or mid-term effects of exosome therapy on cardiac conduction or arrhythmia incidence in animal models, and reported at least one relevant electrophysiological or arrhythmic outcome. Descriptive studies, biomarker-only evaluations, and studies not examining exosomes as a therapeutic intervention were excluded.

RESULTS

The initial search yielded 759 articles (259 from PubMed, 394 from SCOPUS, 106 from ScienceDirect). After removing 68 duplicates and screening titles and abstracts, 77 articles were selected for full-text review. Eighteen studies met the inclusion criteria. Most reported favorable outcomes, including reduced arrhythmia inducibility, improved or restored cardiac conduction, and enhanced overall cardiac function.

CONCLUSION

Preclinical evidence suggests that exosome therapy is potentially effective in reducing arrhythmia burden and improving cardiac electrophysiology, with a favorable safety profile in animal models. Further research is needed to understand its mechanisms deeper, optimize delivery methods, and assess its applicability in human populations.

摘要

引言

尽管治疗策略取得了进展,但心律失常仍然是全球主要的健康问题。在某些临床情况下,新颖且微创的治疗方法尤为可取。外泌体已成为治疗各种疾病的一种有前景的方法,但其在心律失常中的治疗作用仍未得到充分探索。本系统综述旨在综合和评估当前关于基于外泌体的心律失常治疗潜力的证据。

方法

根据PRISMA指南,在PubMed、ScienceDirect和SCOPUS中进行了全面的文献检索,检索词为:(外泌体)AND((心脏传导)或(心律失常))。如果研究调查了外泌体治疗对动物模型心脏传导或心律失常发生率的急性或中期影响,并报告了至少一项相关的电生理或心律失常结果,则纳入研究。排除描述性研究、仅生物标志物评估以及未将外泌体作为治疗干预措施的研究。

结果

初步检索得到759篇文章(259篇来自PubMed,394篇来自SCOPUS,106篇来自ScienceDirect)。去除68篇重复文章并筛选标题和摘要后,77篇文章被选入全文综述。18项研究符合纳入标准。大多数研究报告了良好的结果,包括心律失常诱导性降低、心脏传导改善或恢复以及整体心脏功能增强。

结论

临床前证据表明,外泌体治疗在减轻心律失常负担和改善心脏电生理方面可能有效,在动物模型中具有良好的安全性。需要进一步研究以更深入地了解其机制、优化递送方法并评估其在人群中的适用性。

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本文引用的文献

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Overexpression of Cx43: Is It an Effective Approach for the Treatment of Cardiovascular Diseases?Cx43的过表达:它是治疗心血管疾病的有效方法吗?
Biomolecules. 2025 Mar 4;15(3):370. doi: 10.3390/biom15030370.
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Exosomes Induce Crosstalk Between Multiple Types of Cells and Cardiac Fibroblasts: Therapeutic Potential for Remodeling After Myocardial Infarction.外泌体诱导多种细胞与心肌成纤维细胞之间的串扰:心肌梗死后重塑的治疗潜力。
Int J Nanomedicine. 2024 Oct 19;19:10605-10621. doi: 10.2147/IJN.S476995. eCollection 2024.
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Heart failure and major haemorrhage in people with atrial fibrillation.
心房颤动患者的心力衰竭和主要出血。
Open Heart. 2024 Oct 14;11(2):e002975. doi: 10.1136/openhrt-2024-002975.
4
Cardiac Arrhythmias and Their Management: An In-Depth Review of Current Practices and Emerging Therapies.心律失常及其管理:当前实践与新兴疗法的深入综述
Cureus. 2024 Aug 9;16(8):e66549. doi: 10.7759/cureus.66549. eCollection 2024 Aug.
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2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).2024年欧洲心脏病学会(ESC)心房颤动管理指南,与欧洲心胸外科学会(EACTS)联合制定。
Eur Heart J. 2024 Sep 29;45(36):3314-3414. doi: 10.1093/eurheartj/ehae176.
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Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts.缺氧预处理诱导的成肌细胞来源的外泌体通过增加低温缺血再灌注心脏中Cx43的表达改善心室传导。
Cytotechnology. 2024 Oct;76(5):533-546. doi: 10.1007/s10616-024-00634-1. Epub 2024 May 20.
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Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.通过 IMTP 修饰的牛奶外泌体靶向递送 miR-146a,通过抑制心肌缺血再灌注损伤后的 NF-κB 信号通路发挥心脏保护作用。
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BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization.骨髓间充质干细胞衍生的外泌体介导的 miR-25-3p 传递通过限制 M1 样巨噬细胞极化来保护心肌免受缺血/再灌注损伤。
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