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缺氧预处理间充质干细胞分泌的外泌体通过促进大鼠股骨头坏死血管生成预防激素性股骨头坏死。

Exosomes Secreted from Hypoxia-Preconditioned Mesenchymal Stem Cells Prevent Steroid-Induced Osteonecrosis of the Femoral Head by Promoting Angiogenesis in Rats.

机构信息

Department of Ultrasonography, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.

Department of Sports Medicine, Honghui Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710054, China.

出版信息

Biomed Res Int. 2021 Apr 7;2021:6655225. doi: 10.1155/2021/6655225. eCollection 2021.

DOI:10.1155/2021/6655225
PMID:33928159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8049797/
Abstract

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.

摘要

最近的研究表明,外泌体在再生医学中发挥着与间充质干细胞(MSCs)相似的治疗作用,并且 MSC 来源的外泌体对激素诱导的股骨头坏死(ONFH)具有治疗作用。此外,通过对细胞进行低氧处理可以增强 MSC 来源的外泌体的修复功能。然而,目前尚无关于缺氧预处理的 MSCs 来源的外泌体是否能对激素诱导的 ONFH 显示出更好的治疗效果的相关报道。在体外,我们研究了低氧预处理对大鼠骨髓间充质干细胞(BMMSCs)来源的外泌体的影响以及低氧预处理的 BMMSCs 来源的外泌体的促血管生成能力。在体内,我们研究了低氧预处理的 BMMSCs 来源的外泌体在激素诱导的大鼠 ONFH 模型中对血管生成和保护骨坏死的作用。我们发现,低氧预处理的 BMMSCs 来源的外泌体的促血管生成能力的潜力高于常氧培养的 BMMSCs 来源的外泌体。与常氧培养的 BMMSCs 来源的外泌体相比,低氧预处理的 BMMSCs 来源的外泌体显著促进了人脐静脉内皮细胞(HUVECs)的增殖、迁移、血管内皮生长因子(VEGF)表达和管形成。与常氧培养的 BMMSCs 来源的外泌体相比,低氧预处理的 BMMSCs 来源的外泌体给药显著防止了股骨头的骨丢失并增加了血管体积。总之,我们的数据表明,通过促进血管生成和防止骨丢失,低氧预处理的 BMMSCs 来源的外泌体对激素诱导的 ONFH 发挥更好的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/2e1e906f0276/BMRI2021-6655225.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/28da6eb67240/BMRI2021-6655225.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/08cba6b8505f/BMRI2021-6655225.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/1681dc456935/BMRI2021-6655225.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/3bcb7f580f73/BMRI2021-6655225.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/2e1e906f0276/BMRI2021-6655225.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/28da6eb67240/BMRI2021-6655225.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/08cba6b8505f/BMRI2021-6655225.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/1681dc456935/BMRI2021-6655225.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/3bcb7f580f73/BMRI2021-6655225.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8048/8049797/2e1e906f0276/BMRI2021-6655225.005.jpg

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