制备人羊膜间充质干细胞制剂与质量控制过程中关键问题的思考  

Key problems of preparation and quality control of human amniotic mesenchymal stem cells pharmaceutics

作　　者：王钰莹 余丽梅 Wang Yuying;Yu Limei(Key Laboratory of Cell Engineering of Guizhou Province,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou Province,China;Zunyi City Engineering Research Center of Stem Cell and Regenerative Medicine,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou Province,China)

机构地区：[1]遵义医科大学附属医院贵州省细胞工程重点实验室,贵州省遵义市563003 [2]遵义医科大学附属医院遵义市干细胞与再生医学工程研究中心,贵州省遵义市563003

出　　处：《中国组织工程研究》2022年第25期4016-4021,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(82060270),项目负责人:余丽梅;贵州省人才基地项目(黔人领发[2013]15号),项目负责人:余丽梅;遵义医科大学学术新苗培养及创新探索专项课题(黔科合平台人才[2017]5733-023),项目负责人:王钰莹。

摘　　要：背景:人羊膜间充质干细胞是再生医学理想的种子细胞之一,已在多种疾病治疗中显示了良好的应用前景,对人羊膜间充质干细胞制备关键技术的有效控制,保障制剂符合质量要求,是实现人羊膜间充质干细胞临床应用安全性和有效性的根本。目的:阐述人羊膜间充质干细胞制备与质量控制的关键技术,分析存在的问题和解决策略,总结质量控制关键与技术标准。方法:以“间充质干细胞、细胞培养、生物学特征、质量控制、微生物污染”和“mesenchymal stem cells,cell culture,biological characteristic,quality control,microbiology contamination”为检索词,检索中国知网、万方数据及PubMed数据库2010年1月至2021年3月期间收录的相关文献,最终纳入47篇进行分析。结果与结论:①临床级人羊膜间充质干细胞制备过程中供者的科学选择;采集方法的稳定、规范;细胞分离、培养与体外扩增技术的优化及全过程操作标准化;细胞制备实验室环境的监测及细胞制剂质量检测关键技术均是保证临床使用安全的质量控制的关键;②无血清培养体系的建立与应用,有利于保证制剂质量;③保持人羊膜间充质干细胞生物学特征和功能活性,以及人羊膜间充质干细胞致瘤性、衰老及异常免疫反应等符合放行和复核检验质量标准,能确保人羊膜间充质干细胞制剂发挥良好临床疗效,且最大限度避免发生不良反应。BACKGROUND:Human amniotic mesenchymal stem cells are a kind of the ideal seed cells in the field of regenerative medicine.Human amniotic mesenchymal stem cells have shown good application prospect in the treatment of a variety of diseases.Effective control of the key technology of preparation process to ensure that human amniotic mesenchymal stem cells preparations meet the quality requirements is fundament for the safety and effectiveness of clinical application.OBJECTIVE:To describe the key technologies of human amniotic mesenchymal stem cells preparation and quality control,analyze the existing problems and solutions,and summarize the key quality control and technical standards.METHODS:CNKI,Wanfang,and PubMed databases were retrieved by using computer to search relevant articles published from January 2010 to March 2021 with key words of“mesenchymal stem cells,cell culture,biological characteristic,quality control,microbiology contamination”in Chinese and English,separately.Finally,47 articles were included for analysis.RESULTS AND CONCLUSION:It is the key to quality control and ensure safety in clinic,for example,(1)scientific selection of donors during the preparation of clinical-grade human amniotic mesenchymal stem cells;stable and standardized collection methods;optimization of cell separation,culture,and in vitro expansion techniques,standardization of experimental operations;monitoring of cell preparation laboratory environment,and cell preparation quality detection technology and so on.(2)The establishment and application of a serum-free culture system are conducive to ensuring the quality of preparations.(3)Maintaining the biological characteristics and functional activity of human amniotic mesenchymal stem cells,as well as human amniotic mesenchymal stem cells tumorigenicity,aging,and abnormal immune response meet the release and review inspection quality standards.These can ensure that human amniotic mesenchymal stem cells preparations exert good clinical effects and avoid adverse reactions to t

关 键 词：干细胞 人羊膜间充质干细胞 细胞培养 生物学特征 质量控制 微生物污染 质量检测 安全性评价 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学]