Journal of Prevention and Treatment for Stomatological Diseases ›› 2022, Vol. 30 ›› Issue (9): 609-619.DOI: 10.12016/j.issn.2096-1456.2022.09.001

• Expert Forum • Previous Articles     Next Articles

Advances in isolation and extraction standardization and clinical translation of exosomes

YE Qingsong1,2,3(), PENG Youjian3, LUO Yu1,3   

  1. 1. Department of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China
    2. Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston 02114, USA
    3. Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan 430060, China
  • Received:2021-12-28 Revised:2022-03-24 Online:2022-09-20 Published:2022-06-27
  • Contact: YE Qingsong
  • Supported by:
    National Natural Science Foundation of China(81871503)

细胞外泌体的分离提取标准化及临床转化进展

叶青松1,2,3(), 彭友俭3, 骆瑜1,3   

  1. 1.武汉大学人民医院再生医学中心,湖北 武汉(430060)
    2.哈佛大学麻省总医院,哈佛大学牙学院口腔颌面外科,美国 波士顿(02114)
    3.武汉大学人民医院口腔医学中心,湖北 武汉(430060)
  • 通讯作者: 叶青松
  • 作者简介:叶青松,口腔医学博士,医学科学博士,教授,主任医师,研究员,博士生导师,博士后合作导师。先后于四川大学华西口腔医学院获口腔医学学士、硕士(正畸学方向)和博士(正畸学方向)学位、荷兰格罗宁根大学医学科学博士学位(干细胞与组织工程方向)。曾任澳大利亚詹姆斯库克大学教授、昆士兰大学终身教授、温州医科大学研究员、哈佛大学访问教授。现任武汉大学人民医院再生医学研究中心主任,中国抗衰老促进会创新与应用分会副主席,《NanoTrans Med》(2021-)主编。曾任《Bioactive Materials》专刊主编(2020-2021),澳洲Begg正畸协会执委会常委(2010-),世界牙科研究会FNQ区主席(2014-2016)以及首届亚太正畸与牙周论坛主席(2014)。在临床实践中倡导口腔循证医学,参编人民卫生出版社出版的研究生教材《口腔循证医学》(第1版~第3版)。指导硕士、博士及博士后50余人。在产学研和医疗服务方面都建树颇丰,先后入选英国爱丁堡皇家外科学院院士、英国皇家医学会会士(遴选)、中组部国家特聘青年人才以及国际牙医师学院院士,于2021年获得世界名人录Albert-NelsonMarquis终身成就奖。
  • 基金资助:
    国家自然科学基金项目(81871503)

Abstract:

Exosomes are phospholipid bilayer vesicles secreted by living cells that can carry a variety of signaling molecules, such as RNA, DNA, protein, and lipids. Exosomes play a role in the transmission of signaling molecules between cells, thus regulating many physiological and pathological processes. The methods of extracting exosomes include differential centrifugation, density gradient centrifugation, exclusion chromatography, ultrafiltration, coprecipitation, polymer immune affinity, microfluidic separation technology, etc. Each of these extraction technologies has advantages and disadvantages; however, there is no unified international standard. In addition, the expression of specific proteins and genetic material of exosomes from different cell sources are different; thus, their expression characteristics and functions are also distinctive. Based on this situation, research on exosomes is limited to preclinical studies, and difficulties and challenges still exist in clinical application. This paper summarizes the progress of research in the field of exosomes, to understand the characteristics, modification and application of exosomes from different cell sources, and to summarize their advantages and disadvantages as well as challenges, which can help researchers better understand and master the performance of exosomes. Furthermore, improvement of standard procedures in the extraction and manufacturing of exosomes is important, as it will provide a reference for researchers to carry out exosome-related translational clinical research.

Key words: exosomes, exosomes isolation technique, extraction methods of exosomes, specificity, standardization, exosomes from stem cells, exosomes from tumor cells, preclinical studies, tissue regeneration, targeted drug delivery, tumor resistance

摘要:

外泌体是一类由活细胞分泌的具有磷脂双分子层结构的囊泡,其内携带RNA、DNA、蛋白质、脂质等多种信号分子,起到细胞间信号传递的作用,从而调控生理病理过程。外泌体的提取技术包括差速离心技术、等密度梯度离心技术、尺寸排阻色谱技术、超滤技术、聚合物共沉淀技术、免疫亲和技术、微流控分离技术等,这些提取技术各有优缺点,目前国际上尚未统一外泌体的提取标准;而且不同细胞来源及培养条件下的外泌体其特异性蛋白和遗传物质表达有所不同,从而表现特征和功能也存在差异;因此,目前外泌体多用于临床前研究,广泛应用于临床尚存在困难和挑战。本文总结了外泌体在现阶段研究领域中的进展,归纳了不同细胞来源外泌体的特征和应用、优缺点以及面临的挑战,以期帮助研究者更好地了解和掌握外泌体的性能;同时建议需要完善外泌体提取和制备的标准化流程为外泌体的临床转化和应用提供参考。

关键词: 外泌体, 外泌体分离技术, 细胞外泌体提取技术, 特异性, 标准化, 干细胞外泌体, 肿瘤细胞外泌体, 临床前研究, 组织再生, 靶向药物递送, 肿瘤耐药

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