Chen Shenyuan, Sun Fengtian, Qian Hui, Xu Wenrong, Jiang Jiajia
Aoyang Institute of Cancer, Affiliated Aoyang Hospital of Jiangsu University, 279 Jingang Road, Suzhou, 215600 Jiangsu, China.
Zhenjiang Key Laboratory of High Technology Research on EVs Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, China.
Stem Cells Int. 2022 May 14;2022:1779346. doi: 10.1155/2022/1779346. eCollection 2022.
Mesenchymal stem cells (MSCs) have been widely applied to regenerative medicine owing to their multiple differentiation, self-renewal, and immunomodulatory abilities. Exosomes are cell-secreted natural nanovesicles and thought to be mediators of intercellular communication and material transport. The therapeutic potential of MSCs can be largely attributed to MSC-derived exosomes (MSC-exosomes). Emerging evidence suggests that the therapeutic efficacy of MSC-exosomes is highly dependent on the status of MSCs, and optimization of the extracellular environment affects the exosomal content. Pretreatment methods including three-dimensional cultures, hypoxia, and other biochemical cues have been shown to potentially enhance the biological activity of MSC-exosomes while maintaining or enhancing their production. On the other hand, engineering means to enhance the desired function of MSC-exosomes has been rapidly gaining attention. In particular, biologically active molecule encapsulation and membrane modification can alter or enhance biological functions and targeting of MSC-exosomes. In this review, we summarize two possible strategies to improve the therapeutic activity of MSC-exosomes: preconditioning approaches and engineering exosomes. We also explore the underlying mechanisms of different strategies and discuss their advantages and limitations of the upcoming clinical applications.
间充质干细胞（MSCs）因其多种分化、自我更新和免疫调节能力而被广泛应用于再生医学。外泌体是细胞分泌的天然纳米囊泡，被认为是细胞间通讯和物质运输的介质。MSCs的治疗潜力很大程度上归因于源自MSCs的外泌体（MSC-外泌体）。新出现的证据表明，MSC-外泌体的治疗效果高度依赖于MSCs的状态，细胞外环境的优化会影响外泌体的内容物。包括三维培养、缺氧和其他生化信号在内的预处理方法已被证明有可能增强MSC-外泌体的生物活性，同时维持或提高其产量。另一方面，增强MSC-外泌体所需功能的工程手段也迅速受到关注。特别是，生物活性分子封装和膜修饰可以改变或增强MSC-外泌体的生物学功能和靶向性。在这篇综述中，我们总结了两种改善MSC-外泌体治疗活性的可能策略：预处理方法和工程化外泌体。我们还探讨了不同策略的潜在机制，并讨论了它们在即将到来的临床应用中的优缺点。
