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脂肪间充质干细胞来源的外泌体通过激活PI3K/AKT信号通路增强PC12细胞功能。

Adipose Mesenchymal Stem Cell-Derived Exosomes Enhance PC12 Cell Function through the Activation of the PI3K/AKT Pathway.

作者信息

Xie Yong, Chen Yangping, Zhu Yuyuan, Chen Xia, Lin Tiecheng, Zhou Dan

机构信息

Department of Obstetrics and Gynecology, The First People's Hospital of Foshan, Foshan 528000, China.

Department of Galactophore Surgery, The First People's Hospital of Foshan, Foshan 528000, China.

出版信息

Stem Cells Int. 2021 Oct 15;2021:2229477. doi: 10.1155/2021/2229477. eCollection 2021.


DOI:10.1155/2021/2229477
PMID:34691190
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8536463/
Abstract

Transplantation of mesenchymal stem cells has been considered as an auspicious treatment for repairing nerve injuries. The rat adrenal pheochromocytoma cell line (PC12) is one of the traditional models for the study of neuronal differentiation and neuroregeneration in vitro. However, the effects of adipose mesenchymal stem cell-derived exosomes (ADSC-exo) on PC12 cells remain unclear and to be elucidated. In our study, the effects of ADSC-exo on PC12 cells were investigated. ADSC-exo were isolated by ultracentrifugation and characterized by transmission electron microscopy, flow nanoanalysis, and western blot. The effects of ADSC-exo on PC12 cell proliferation, migration, apoptosis, and the protein levels were analyzed using CCK-8 assay and EdU incorporation assay, transwell migration assay and scratch wound assay, flow cytometry, and western blot, respectively. We successfully isolated and purified exosomes from ADSC supernatant and found that ADSC-exo treatment significantly promoted PC12 cell proliferation and migration, inhibited their apoptosis, and activated the PI3K/AKT pathway, while PI3K/AKT signaling repression using LY294002 exhibited the opposite effects. The results showed that ADSC-exo promoted proliferation and migration and inhibited apoptosis of PC12 through the activation of the PI3K/AKT pathway. Thus, the effect of ADSC-exo on PC12 cells may suggest ADSC-exo may be a promising therapeutic for nerve damage.

摘要

间充质干细胞移植已被视为修复神经损伤的一种有前景的治疗方法。大鼠肾上腺嗜铬细胞瘤细胞系(PC12)是体外研究神经元分化和神经再生的传统模型之一。然而,脂肪间充质干细胞衍生的外泌体(ADSC-exo)对PC12细胞的影响仍不清楚,有待阐明。在我们的研究中,研究了ADSC-exo对PC12细胞的影响。通过超速离心分离ADSC-exo,并通过透射电子显微镜、流式纳米分析和蛋白质印迹进行表征。分别使用CCK-8法和EdU掺入法、Transwell迁移试验和划痕试验、流式细胞术和蛋白质印迹分析ADSC-exo对PC12细胞增殖、迁移、凋亡和蛋白质水平的影响。我们成功地从ADSC上清液中分离和纯化了外泌体,发现ADSC-exo处理显著促进PC12细胞增殖和迁移,抑制其凋亡,并激活PI3K/AKT通路,而使用LY294002抑制PI3K/AKT信号则表现出相反的效果。结果表明,ADSC-exo通过激活PI3K/AKT通路促进PC12细胞的增殖和迁移并抑制其凋亡。因此,ADSC-exo对PC12细胞的作用可能表明ADSC-exo可能是一种有前途的神经损伤治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/c1bf0a11f290/SCI2021-2229477.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/a4db595ddb80/SCI2021-2229477.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/ad32b85fb09f/SCI2021-2229477.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/a2517478989a/SCI2021-2229477.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/86707f596090/SCI2021-2229477.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/7472da527451/SCI2021-2229477.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/cd065384f4ba/SCI2021-2229477.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/c1bf0a11f290/SCI2021-2229477.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/a4db595ddb80/SCI2021-2229477.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/ad32b85fb09f/SCI2021-2229477.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/a2517478989a/SCI2021-2229477.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/86707f596090/SCI2021-2229477.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/7472da527451/SCI2021-2229477.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/cd065384f4ba/SCI2021-2229477.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02f7/8536463/c1bf0a11f290/SCI2021-2229477.007.jpg

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[3]
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[4]
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J Transl Med. 2025-1-3

[5]
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Int J Mol Sci. 2024-7-18

[6]
Role of mesenchymal stem cell-derived exosomes in the regeneration of different tissues.

J Biol Eng. 2024-6-6

[7]
Stem cell exosome-loaded Gelfoam improves locomotor dysfunction and neuropathic pain in a rat model of spinal cord injury.

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[8]
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[10]
Global trends and current status in pheochromocytoma: a bibliometric analysis of publications in the last 20 years.

Front Endocrinol (Lausanne). 2023

本文引用的文献

[1]
Manufacturing and banking canine adipose-derived mesenchymal stem cells for veterinary clinical application.

BMC Vet Res. 2021-3-1

[2]
Mesenchymal Stem Cells Transplantation for Neuropathic Pain Induced By Peripheral Nerve Injury in Animal Models: A Systematic Review.

Stem Cells Dev. 2020-11-15

[3]
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Burns Trauma. 2020-2-27

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Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis?

Stem Cell Res Ther. 2019-11-21

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[7]
Mesenchymal stromal cell secretome as a therapeutic strategy for traumatic brain injury.

Biofactors. 2019-9-9

[8]
Mesenchymal stem cell-derived exosomes for clinical use.

Bone Marrow Transplant. 2019-8

[9]
The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells: a comprehensive review.

Stem Cell Res Ther. 2019-8-7

[10]
Nerve-sparing radical hysterectomy: steps to standardize surgical technique.

Int J Gynecol Cancer. 2019-9

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