中国组织工程研究

中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (7): 1118-1123.doi: 10.12307/2024.111

• 干细胞综述 stem cell review • 上一篇    下一篇

人造外泌体治疗心肌梗死：应用现状及前景

刘瀚峰，王晶晶，余云生   

  1. 苏州大学附属第一医院心脏大血管外科，江苏省苏州市   215000
  • 收稿日期:2023-01-12 接受日期:2023-03-23 出版日期:2024-03-08 发布日期:2023-07-17
  • 通讯作者: 余云生，博士，主任医师，副教授，硕士生导师，苏州大学附属第一医院心脏大血管外科，江苏省苏州市 215000
  • 作者简介:刘瀚峰，男，1997 年生，四川省人，汉族，苏州大学在读硕士，主要从事心脏大血管疾病的临床和基础研究。
  • 基金资助:
    江苏省卫生健康委科研项目(ZDA2020017)，项目负责人：余云生

Artificial exosomes in treatment of myocardial infarction: current status and prospects

Liu Hanfeng, Wang Jingjing, Yu Yunsheng   

  1. Department of Cardiovascular Surgery, First Affiliated Hospital, Soochow University, Suzhou 215000, Jiangsu Province, China
  • Received:2023-01-12 Accepted:2023-03-23 Online:2024-03-08 Published:2023-07-17
  • Contact: Yu Yunsheng, MD, Chief physician, Associate professor, Master’s supervisor, Department of Cardiovascular Surgery, First Affiliated Hospital, Soochow University, Suzhou 215000, Jiangsu Province, China
  • About author:Liu Hanfeng, Master candidate, Department of Cardiovascular Surgery, First Affiliated Hospital, Soochow University, Suzhou 215000, Jiangsu Province, China
  • Supported by:
    Scientific Research Project of Jiangsu Provincial Health Commission, No. ZDA2020017 (to YYS)

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摘要：


文题释义：

人造外泌体：基于天然外泌体存在的制备难度大、储存困难以及生物靶向性较差等缺陷，通过纳米工程技术进行如表面修饰、药物装载及生物膜杂交等方式改造外泌体，或仿照外泌体结构功能生产仿生外泌体，研究者们将这些纳米颗粒称为人造外泌体，也有学者表述为“纳米囊泡(nanovesicles)”“外泌体模拟物(exosome-mimetics)”“杂交外泌体(hybrid exosomes)”等。
心肌梗死：由于冠状动脉供血中断，致供血区持续缺血而导致的较大范围的心肌坏死。临床上有剧烈而较持久的胸骨后疼痛，用硝酸酯类制剂或休息后症状不能完全缓解，可并发心律失常、休克或心力衰竭。


背景：心肌梗死是目前最严重的心血管疾病之一，现有的临床治疗方案如溶栓治疗、经皮冠状动脉介入治疗和冠状动脉旁路移植术均无法完全恢复缺血造成的心肌损伤。干细胞来源的外泌体治疗心肌梗死是近年来的研究热点，但天然来源的外泌体产量少，获取难度大、耗时长、归巢效果不佳等限制了其临床应用。在这种情况下，构建人造外泌体作为天然外泌体的替代品已成为解决上述问题的有效策略。

目的：阐述人造外泌体在治疗心肌梗死中的研究现状，将其分为半人造和全人造两种设计模式，就两种模式的研究进展及存在的问题展开讨论，最后对其在未来的临床应用做出评价和展望。
方法：以“人造外泌体，心肌梗死，工程化”为中文检索词，以“artificial exosome，hybrid exosome，myocardial infarction，nanoparticle，drug delivery system”为英文检索词，检索PubMed和中国知网数据库的相关文献。检索时限重点为2017年1月至2022年12月，同时纳入部分经典远期文献。通过阅读文题和摘要进行初步筛选；排除重复性研究、低质量期刊及内容不相关的文献，最后纳入73篇文献进行综述。

结果与结论：①通过半人造改造外泌体的方式，不论是靶向肽段的修饰、生物膜的杂交或是磁力物质的辅助，均改善了传统的外泌体疗法靶向性不足、驻留率低、易被网状内皮系统所清除等缺陷，提高了传统外泌体治疗心肌梗死的效率，但是这些改造策略存在修饰效率不明确、医学伦理以及生物毒性等方面的问题。②全人造仿生外泌体相对于外泌体的改造，其设计自由度较高，可以解决天然来源外泌体提取存储难度高、规模化生产局限等问题，然而全人造外泌体的改造策略目前仍缺少可靠的临床前数据支持与生物安全性的检测，尚未形成规模化生产所需的标准化流程，因此在应用到临床以前，作为替代天然外泌体的人造外泌体方案仍需要科研人员进行持续深入研究。

https://orcid.org/0009-0003-7338-552X (刘瀚峰)；https://orcid.org/0000-0001-5822-4443 (余云生)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 人造外泌体, 干细胞, 心肌梗死, 缺血性心脏病, 非细胞疗法, 生物工程技术, 药物递送系统, 细胞外囊泡, 仿生纳米技术

Abstract: BACKGROUND: Myocardial infarction is one of the most serious cardiovascular diseases at present, and the existing clinical treatment options such as thrombolytic therapy, percutaneous coronary intervention and coronary artery bypass grafting cannot fully restore the myocardial damage caused by ischemia. Stem cell-derived exosomes for the treatment of myocardial infarction have been a hot research topic in recent years, but the low yield of natural-derived exosomes, the difficulty and time consuming nature of obtaining them, and the poor homing effect have limited their clinical application. In this context, the construction of artificial exosomes as an alternative to natural exosomes has become an effective strategy to solve the above problems.  
OBJECTIVE: To expound the research status of artificial exosomes in the treatment of myocardial infarction, and classify them into two design modes: semi-artificial and full-artificial, and discuss the research progress and problems of the two modes, finally, make the evaluation and prospect of its clinical application in the future.
METHODS: PubMed and CNKI were searched for relevant articles with “artificial exosomes, myocardial infarction, engineering” in Chinese, and “artificial exosome, hybrid exosome, myocardial infarction, nanoparticle, drug delivery system” in English. The focus of the search was from January 2017 to December 2022, and some of the classic forward literature was included. A preliminary selection was conducted through reading titles and abstracts. Repetitive studies, low-quality journals and irrelevant articles were excluded. Finally, 73 articles were included for review.  
RESULTS AND CONCLUSION: (1) By semi-artificially modifying exosomes, whether it is the modification of targeting peptides, hybridization of biofilms or the assistance of magnetic substances, traditional exosome therapies with insufficient targeting and low retention rate and easy to be cleared by the reticuloendothelial system have improved the efficiency of traditional exosome therapy for myocardial infarction. However, these strategies have problems such as unclear modification efficiency, medical ethics, and biotoxicity. (2) Fully artificial bionic exosomes have a higher degree of design freedom compared to exosome modification, which can solve the problems of high extraction and storage difficulties of exosomes of natural origin and limitations of large-scale production; however, this artificial exosome strategy still lacks reliable preclinical data support and biosafety testing, and has not yet formed a standardized process required for large-scale production; therefore, before applying to the clinic, the artificial exosome solution as an alternative to natural exosomes still needs continuous in-depth research by researchers.

Key words: artificial exosome, stem cell, myocardial infarction, ischemic heart disease, non-cellular therapy, bioengineering technology, drug delivery system, extracellular vesicle, biomimetic nanotechnology

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