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外泌体疗法中细胞的动态纳米力学表征

Dynamic nanomechanical characterization of cells in exosome therapy.

作者信息

Chen Ye, Zhang Zihan, Li Ziwei, Wu Wenjie, Lan Shihai, Yan Tianhao, Mei Kainan, Qiao Zihan, Wang Chen, Bai Chuanbiao, Li Ziyan, Wu Shangquan, Wang Jianye, Zhang Qingchuan

机构信息

CAS Key Laboratory of Mechanical Behavior and Design of Material, Department of Modern Mechanics, University of Science and Technology of China, Hefei, Anhui 230027 China.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022 China.

出版信息

Microsyst Nanoeng. 2024 Jul 15;10:97. doi: 10.1038/s41378-024-00735-z. eCollection 2024.

Abstract

Exosomes derived from mesenchymal stem cells (MSCs) have been confirmed to enhance cell proliferation and improve tissue repair. Exosomes release their contents into the cytoplasmic solution of the recipient cell to mediate cell expression, which is the main pathway through which exosomes exert therapeutic effects. The corresponding process of exosome internalization mainly occurs in the early stage of treatment. However, the therapeutic effect of exosomes in the early stage remains to be further studied. We report that the three-dimensional cell traction force can intuitively reflect the ability of exosomes to enhance the cytoskeleton and cell contractility of recipient cells, serving as an effective method to characterize the therapeutic effect of exosomes. Compared with traditional biochemical methods, we can visualize the early therapeutic effect of exosomes in real time without damage by quantifying the cell traction force. Through quantitative analysis of traction forces, we found that endometrial stromal cells exhibit short-term cell roundness accompanied by greater traction force during the early stage of exosome therapy. Further experiments revealed that exosomes enhance the traction force and cytoskeleton by regulating the Rac1/RhoA signaling pathway, thereby promoting cell proliferation. This work provides an effective method for rapidly quantifying the therapeutic effects of exosomes and studying the underlying mechanisms involved.

摘要

源自间充质干细胞(MSC)的外泌体已被证实可增强细胞增殖并改善组织修复。外泌体将其内容物释放到受体细胞的细胞质溶液中以介导细胞表达,这是外泌体发挥治疗作用的主要途径。外泌体内化的相应过程主要发生在治疗早期。然而,外泌体在早期的治疗效果仍有待进一步研究。我们报告三维细胞牵引力可以直观地反映外泌体增强受体细胞细胞骨架和细胞收缩力的能力,作为表征外泌体治疗效果的有效方法。与传统生化方法相比,我们可以通过量化细胞牵引力实时可视化外泌体的早期治疗效果而不造成损伤。通过对牵引力的定量分析,我们发现子宫内膜基质细胞在接受外泌体治疗的早期表现出短期的细胞圆度并伴有更大的牵引力。进一步的实验表明,外泌体通过调节Rac1/RhoA信号通路增强牵引力和细胞骨架,从而促进细胞增殖。这项工作为快速量化外泌体的治疗效果和研究其中涉及的潜在机制提供了一种有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a70/11251037/453f854d0db0/41378_2024_735_Fig1_HTML.jpg

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