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脂肪干细胞衍生的细胞外囊泡通过内化诱导许旺细胞增殖。

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization.

机构信息

Research Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.

出版信息

Cells. 2020 Jan 9;9(1):163. doi: 10.3390/cells9010163.

DOI:10.3390/cells9010163
PMID:31936601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7016740/
Abstract

Recent studies showed a beneficial effect of adipose stem cell-derived extracellular vesicles (ADSC-EVs) on sciatic nerve repair, presumably through Schwann cell (SC) modulation. However, it has not yet been elucidated whether ADSC-EVs exert this supportive effect on SCs by extracellular receptor binding, fusion to the SC membrane, or endocytosis mediated internalization. ADSCs, ADSC-EVs, and SCs were isolated from rats and characterized according to associated marker expression and properties. The proliferation rate of SCs in response to ADSC-EVs was determined using a multicolor immunofluorescence staining panel followed by automated image analysis. SCs treated with ADSC-EVs and silica beads were further investigated by 3-D high resolution confocal microscopy and live cell imaging. Our findings demonstrated that ADSC-EVs significantly enhanced the proliferation of SCs in a time- and dose-dependent manner. 3-D image analysis revealed a perinuclear location of ADSC-EVs and their accumulation in vesicular-like structures within the SC cytoplasm. Upon comparing intracellular localization patterns of silica beads and ADSC-EVs in SCs, we found striking resemblance in size and distribution. Live cell imaging visualized that the uptake of ADSC-EVs preferentially took place at the SC processes from which the EVs were transported towards the nucleus. This study provided first evidence for an endocytosis mediated internalization of ADSC-EVs by SCs and underlines the therapeutic potential of ADSC-EVs in future approaches for nerve regeneration.

摘要

最近的研究表明脂肪干细胞衍生的细胞外囊泡 (ADSC-EVs) 对坐骨神经修复具有有益作用,可能通过施万细胞 (SC) 调节。然而,目前尚不清楚 ADSC-EVs 是否通过细胞外受体结合、融合到 SC 膜或内吞介导的内化来对 SC 发挥这种支持作用。从大鼠中分离 ADSC、ADSC-EVs 和 SC,并根据相关标志物表达和特性进行鉴定。通过多色免疫荧光染色面板和自动图像分析确定 SC 对 ADSC-EVs 的增殖率。用 ADSC-EVs 和硅胶珠处理 SC 后,通过 3-D 高分辨率共聚焦显微镜和活细胞成像进一步研究。我们的研究结果表明,ADSC-EVs 以时间和剂量依赖的方式显著增强了 SC 的增殖。3-D 图像分析显示 ADSC-EVs 位于核周位置,并在 SC 细胞质中的囊泡样结构中积累。在比较 SC 中硅胶珠和 ADSC-EVs 的细胞内定位模式时,我们发现它们在大小和分布上非常相似。活细胞成像可视化表明,ADSC-EVs 的摄取优先发生在 SC 过程中,EV 从这些过程中被运输到细胞核。这项研究首次提供了 ADSC-EVs 通过 SC 内吞摄取的证据,并强调了 ADSC-EVs 在未来神经再生方法中的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/0d3cf5312d2f/cells-09-00163-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/5f85cd29588f/cells-09-00163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/26d99aeb17ac/cells-09-00163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/43be444ff9ed/cells-09-00163-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/2670bd324c96/cells-09-00163-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/e28b97156fb0/cells-09-00163-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/0d3cf5312d2f/cells-09-00163-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/5f85cd29588f/cells-09-00163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/26d99aeb17ac/cells-09-00163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/43be444ff9ed/cells-09-00163-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/2670bd324c96/cells-09-00163-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/e28b97156fb0/cells-09-00163-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e05/7016740/0d3cf5312d2f/cells-09-00163-g006.jpg

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