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骨髓间充质干细胞来源的小细胞外囊泡的成骨和成血管作用在激素性股骨头坏死中减弱。

The Proosteogenic and Proangiogenic Effects of Small Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Are Attenuated in Steroid-Induced Osteonecrosis of the Femoral Head.

机构信息

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

Department of Joint Surgery, Honghui Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710054, China.

出版信息

Biomed Res Int. 2020 May 6;2020:4176926. doi: 10.1155/2020/4176926. eCollection 2020.

DOI:10.1155/2020/4176926
PMID:32461986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7229539/
Abstract

Small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (BMMSCs) from individuals with steroid-induced osteonecrosis of the femoral head (ONFH) have not been studied. The objective of the present study was to compare the proosteogenic and proangiogenic effects of sEVs derived from BMMSCs from rats with steroid-induced ONFH (oBMMSCs-sEVs) and sEVs derived from BMMSCs from normal rats (nBMMSCs-sEVs). BMMSCs were isolated from steroid-induced ONFH rats and healthy rats. sEVs were isolated and characterized by Western blotting analysis of exosomal surface biomarkers and by transmission electron microscopy. The impacts of nBMMSCs-sEVs and oBMMSCs-sEVs on the proliferation and osteogenic differentiation of BMMSCs were determined via cell proliferation assay, alizarin red staining, and alkaline phosphatase activity assay. Enzyme-linked immunosorbent assay and tube formation assay were conducted to investigate the effect of nBMMSCs-sEVs and oBMMSCs-sEVs on the angiogenic potential of human umbilical vein endothelial cells (HUVECs). The expression of relevant genes was detected by quantitative real-time polymerase chain reaction analysis, and the expression of -catenin was detected by immunofluorescence. Both nBMMSCs-sEVs and oBMMSCs-sEVs promoted proliferation, osteogenic differentiation, and -catenin expression of BMMSCs and enhanced angiogenesis of HUVECs. However, compared with nBMMSCs-sEVs, oBMMSCs-sEVs exhibited attenuated effects. Our findings indicated that the proosteogenic and proangiogenic effects of sEVs were partially attenuated in steroid-induced ONFH. Therefore, this study might offer guidance for the selection of source cells for sEV therapy in the future.

摘要

目前尚未研究过来源于激素诱导性股骨头坏死（ONFH）患者骨髓间充质干细胞（BMMSCs）的小细胞外囊泡（sEVs）。本研究旨在比较来源于激素诱导性 ONFH 大鼠 BMMSCs 的 sEVs（oBMMSCs-sEVs）和来源于正常大鼠 BMMSCs 的 sEVs（nBMMSCs-sEVs）的成骨和成血管作用。从激素诱导性 ONFH 大鼠和健康大鼠中分离 BMMSCs。通过 Western blot 分析外泌体表面标志物和透射电子显微镜对 sEVs 进行分离和鉴定。通过细胞增殖试验、茜素红染色和碱性磷酸酶活性测定来确定 nBMMSCs-sEVs 和 oBMMSCs-sEVs 对 BMMSCs 增殖和成骨分化的影响。通过酶联免疫吸附试验和管形成试验来研究 nBMMSCs-sEVs 和 oBMMSCs-sEVs 对人脐静脉内皮细胞（HUVECs）成血管潜能的影响。通过定量实时聚合酶链反应分析检测相关基因的表达，并通过免疫荧光检测 -连环蛋白的表达。nBMMSCs-sEVs 和 oBMMSCs-sEVs 均促进 BMMSCs 的增殖、成骨分化和 -连环蛋白表达，并增强 HUVECs 的血管生成。然而，与 nBMMSCs-sEVs 相比，oBMMSCs-sEVs 的作用减弱。本研究表明，sEVs 的成骨和成血管作用在激素诱导性 ONFH 中部分减弱。因此，本研究可能为未来 sEV 治疗中源细胞的选择提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/300857d66fd6/BMRI2020-4176926.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/ffa796d2006b/BMRI2020-4176926.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/8558955beab2/BMRI2020-4176926.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/c26a5d3ffbd3/BMRI2020-4176926.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/300857d66fd6/BMRI2020-4176926.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/ffa796d2006b/BMRI2020-4176926.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/8558955beab2/BMRI2020-4176926.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/c26a5d3ffbd3/BMRI2020-4176926.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d274/7229539/300857d66fd6/BMRI2020-4176926.004.jpg

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Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.人脂肪组织来源间充质干细胞衍生的外泌体通过诱导特应性皮炎中神经酰胺的从头合成促进表皮屏障修复。
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The Role of Mesenchymal Stem Cell Secretome (Extracellular Microvesicles and Exosomes) in Animals' Musculoskeletal and Neurologic-Related Disorders.间充质干细胞分泌组（细胞外微泡和外泌体）在动物肌肉骨骼及神经相关疾病中的作用
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