Huang Chun-Chieh, Kang Miya, Narayanan Raghuvaran, DiPietro Luisa A, Cooper Lyndon F, Gajendrareddy Praveen, Ravindran Sriram
Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL, United States.
Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, United States.
Front Pharmacol. 2020 Mar 3;11:163. doi: 10.3389/fphar.2020.00163. eCollection 2020.
Mesenchymal stem cells (MSCs) are multipotent cells with regenerative and immunomodulatory properties. Several aspects of MSC function have been attributed to the paracrine effects of MSC derived extracellular vesicles (EVs). Although MSC EVs show great promise for regenerative medicine applications, insights into their uptake mechanisms by different target cells and the ability to control MSC EV properties for defined function have remained elusive knowledge gaps. The primary goal of this study is to elucidate how the basic properties of MSC derived EVs can be exploited for function-specific activity in regenerative medicine. Our first important observation is that, MSC EVs possess a common mechanism of endocytosis across multiple cell types. Second, altering the MSC state by inducing differentiation into multiple lineages did not affect the exosomal properties or endocytosis but triggered the expression of lineage-specific genes and proteins and respectively. Overall, the results presented in this study show a common mechanism of endocytosis for MSC EVs across different cell types and the feasibility to generate functionally enhanced EVs by modifications to parental MSCs.
间充质干细胞（MSCs）是具有再生和免疫调节特性的多能细胞。MSC功能的几个方面归因于MSC衍生的细胞外囊泡（EVs）的旁分泌作用。尽管MSC EVs在再生医学应用中显示出巨大潜力，但对于它们被不同靶细胞摄取的机制以及控制MSC EV特性以实现特定功能的能力，仍然存在难以捉摸的知识空白。本研究的主要目标是阐明如何利用MSC衍生EVs的基本特性在再生医学中实现功能特异性活性。我们的第一个重要观察结果是，MSC EVs在多种细胞类型中具有共同的内吞作用机制。其次，通过诱导分化为多种谱系来改变MSC状态，并不影响外泌体特性或内吞作用，但分别触发了谱系特异性基因和蛋白质的表达。总体而言，本研究呈现的结果表明，MSC EVs在不同细胞类型中具有共同的内吞作用机制，并且通过对亲代MSC进行修饰来生成功能增强的EVs是可行的。
