Huang Chun-Chieh, Kang Miya, Leung Kasey, Lu Yu, Shirazi Sajjad, Gajendrareddy Praveen, Ravindran Sriram
Department of Oral Biology, University of Illinois Chicago, Chicago, Illinois, United States.
Department of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, Illinois, United States.
Front Cell Dev Biol. 2023 Feb 8;11:1127594. doi: 10.3389/fcell.2023.1127594. eCollection 2023.
Mesenchymal stem cell derived extracellular vesicles (MSC EVs) possess excellent immunomodulatory and therapeutic properties. While beneficial, from a translational perspective, extracellular vesicles with consistent functionality and target specificity are required to achieve the goals of precision medicine and tissue engineering. Prior research has identified that the miRNA composition of mesenchymal stem cell derived extracellular vesicles contributes significantly towards extracellular vesicles functionality. In this study, we hypothesized that mesenchymal stem cell derived extracellular vesicle functionality can be rendered pathway-specific using a miRNA-based extracellular vesicles engineering approach. To test this hypothesis, we utilized bone repair as a model system and the BMP2 signaling cascade as the targeted pathway. We engineered mesenchymal stem cell extracellular vesicles to possess increased levels of miR-424, a potentiator of the BMP2 signaling cascade. We evaluated the physical and functional characteristics of these extracellular vesicles and their enhanced ability to trigger the osteogenic differentiation of naïve mesenchymal stem cell and facilitate bone repair Results indicated that the engineered extracellular vesicles retained their extracellular vesicles characteristics and endocytic functionality and demonstrated enhanced osteoinductive function by activating SMAD1/5/8 phosphorylation and mesenchymal stem cell differentiation and enhanced bone repair Furthermore, the inherent immunomodulatory properties of the mesenchymal stem cell derived extracellular vesicles remained unaltered. These results serve as a proof-of-concept for miRNA-based extracellular vesicles engineering approaches for regenerative medicine applications.
间充质干细胞衍生的细胞外囊泡(MSC EVs)具有出色的免疫调节和治疗特性。虽然有益,但从转化医学的角度来看,需要具有一致功能和靶标特异性的细胞外囊泡来实现精准医学和组织工程的目标。先前的研究已经确定,间充质干细胞衍生的细胞外囊泡的miRNA组成对细胞外囊泡的功能有显著贡献。在本研究中,我们假设可以使用基于miRNA的细胞外囊泡工程方法使间充质干细胞衍生的细胞外囊泡功能具有途径特异性。为了验证这一假设,我们将骨修复作为模型系统,将BMP2信号级联作为靶向途径。我们对间充质干细胞外囊泡进行工程改造,使其具有更高水平的miR-424,miR-424是BMP2信号级联的增强剂。我们评估了这些细胞外囊泡的物理和功能特性,以及它们触发未处理的间充质干细胞成骨分化和促进骨修复的增强能力。结果表明,工程化的细胞外囊泡保留了其细胞外囊泡特征和内吞功能,并通过激活SMAD1/5/8磷酸化和间充质干细胞分化表现出增强的骨诱导功能以及增强的骨修复能力。此外,间充质干细胞衍生的细胞外囊泡固有的免疫调节特性保持不变。这些结果为基于miRNA的细胞外囊泡工程方法在再生医学应用中提供了概念验证。
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