调整细胞培养条件提高间充质干细胞外泌体治疗骨关节炎的潜能  

Enhancing potential of mesenchymal stem cell exosomes for osteoarthritis by adjusting cell culture condition

作　　者：钱燕 刘启颂 Qian Yan;Liu Qisong(National Clinical Research Center for Infectious Diseases,Shenzhen Third People’s Hospital,Southern University of Science and Technology,Shenzhen 518112,Guangdong Province,China)

机构地区：[1]深圳国家感染性疾病临床医学研究中心,南方科技大学深圳市第三人民医院,广东省深圳市518112

出　　处：《中国组织工程研究》2025年第1期164-174,共11页Chinese Journal of Tissue Engineering Research

基　　金：深圳市科创委基础研究专项(自然科学基金)(JCYJ20210324113401003);项目负责人:刘启颂。

摘　　要：背景:间充质干细胞外泌体有望发展成为治疗骨关节炎的无细胞疗法,而通过调整细胞培养条件,可以进一步提高其治疗活性和临床转化潜能。目的:综述分析细胞培养条件对外泌体活性的影响,分析其临床转化潜力。方法:查阅国内外有关骨关节炎/软骨损伤修复与间充质干细胞来源外泌体的文献。检索词分别为“外泌体,间充质干细胞,骨关节炎,软骨修复”和“exosomes,extracellular vesicles,mesenchymal stem cells,osteoarthritis,cartilage repair”,检索数据库分别为PubMed和中国知网数据库,检索时限为2010-2023年,最后纳入100篇文献进行总结和分析。结果与结论:(1)在间充质干细胞的培养过程中,提供有利于软骨细胞生长的物理环境,或添加软骨保护小分子、成软骨诱导因子和炎症因子等刺激细胞,可以进一步提高间充质干细胞外泌体在维持软骨细胞表型、促进软骨再生和免疫抑制等方面的调控活性;因此,其他具有相似特征的物理或化学因素,也有可能提升间充质干细胞外泌体治疗骨关节炎的疗效。(2)低氧诱导、脉冲电磁场刺激、生物反应器及软骨保护分子(如人甲状旁腺素1-34)刺激等细胞培养方案具有安全、可规模化生产等优点,可用于制备临床用途的、疗效好的间充质干细胞外泌体。(3)间充质干细胞外泌体有望实现骨关节炎的修正治疗,通过调整细胞培养方案提升治疗活性,可进一步提高其临床转化的可行性。BACKGROUND:Exosomes derived from mesenchymal stem cells are prospective cell-free alternatives for treating osteoarthritis.Their therapeutic activity and clinical transformation potential can be further improved by adjusting cell culture condition.OBJECTIVE:To review the effect of cell culture conditions on exosome activity and to analyze its clinical transformation potential.METHODS:Articles concerning osteoarthritis/cartilage repair and mesenchymal stem cell-derived exosomes were retrieved on CNKI and PubMed using“exosomes,mesenchymal stem cells,osteoarthritis or cartilage repair”as Chinese search terms and“exosomes or extracellular vesicles,mesenchymal stem cells,osteoarthritis or cartilage repair”as English search terms.The search time was from 2010 to 2023.Finally,100 articles were included for summary and analysis.RESULTS AND CONCLUSION:(1)During cell culture,providing a physical environment favorable for chondrocyte growth or adding chondroprotective small molecules,chondrogenic factors,or inflammatory factors,can further improve the regulatory activity of exosomes secreted by mesenchymal stem cells in maintaining chondrocyte phenotype,promoting cartilage regeneration,and immunosuppression.Therefore,other physical or chemical factors with similar characteristics may also improve the effects of exosomes secreted by mesenchymal stem cells for treating osteoarthritis.(2)Some treatments during cell culture,such as hypoxia induction,pulsed electromagnetic field stimulation,bioreactor,and chondroprotective molecule(e.g.,human parathyroid hormone 1-34)stimulation are safe and scalable,which allows for the production of clinical-grade exosomes secreted by mesenchymal stem cells for osteoarthritis treatment.(3)Mesenchymal stem cell exosomes are expected to achieve modified treatment of osteoarthritis,and the feasibility of clinical transformation can be further improved by adjusting the cell culture regimen to enhance the therapeutic activity.

关 键 词：间充质干细胞 外泌体 骨关节炎 软骨修复 细胞培养 低氧诱导 预处理 三维培养 软骨保护因子 炎症因子 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364