Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R
Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R
复制标题
来自缺氧处理的人脂肪间充质干细胞的外泌体通过 VEGF/VEGF-R 增强血管生成
DOI：
10.1016/j.biocel.2019.01.017
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发表时间：
2019-04-01
影响因子：
4
通讯作者：
Han, Yan
中科院分区：
文献类型：
--
作者：
Han, Yudi;Ren, Jing;Han, Yan
背景资料：我们先前报道了来自低氧预处理的脂肪间充质干细胞（ADSC）的外泌体的共移植改善了移植组织的新血管生成和存活。方法：从常氧处理（nADSC-Exo）或低氧处理（hypADSC-Exo）的人ADSC中收集Exosomes，并在人脐静脉内皮细胞（HUVECs）和裸鼠皮下脂肪移植模型中评价其促血管生成能力。结果：与nADSC-Exo组和未处理对照组相比，hypADSC-Exo处理组HUVECs的增殖、迁移和管形成能力明显增强。蛋白质芯片显示，hypADSC-Exo中血管内皮生长因子（VEGF）、表皮生长因子（EGF）、成纤维细胞生长因子（FGF）及其受体（VEGF-R2、VEGF-R3）和单核细胞趋化蛋白2（MCP-2）、单核细胞趋化蛋白4（MCP-4）的表达水平均显著高于nADSC-Exo。在裸鼠脂肪移植模型中，CD 31的免疫荧光显示hypADSC-Exo显著改善移植物周围的新血管形成。此外，与nADSC-Exo和对照组相比，hypADSC-Exo共移植在移植后30天显著增加移植组织中EGF、FGF、VEGF/VEGF-R、血管生成素-1（Ang-1）和具有免疫球蛋白样和EGF样结构域1的酪氨酸激酶（Tie-1，血管生成素受体）的蛋白表达。免疫组织化学分析表明，hypADSC-Exo治疗显着增加VEGF-R的表达在移植tissue.Conclusions：来自低氧处理的人ADSC的外泌体具有更高的能力，以增强脂肪移植血管生成，至少部分，通过调节VEGF/VEGF-R信号。
Background: We previously reported that co-transplantation of exosomes from hypoxia-preconditioned adipose mesenchymal stem cells (ADSCs) improves the neoangiogenesis and survival of the grafted tissue. This study aimed to investigate the molecular mechanism of this protective effect.Methods: Exosomes were collected from normoxia-treated (nADSC-Exo) or hypoxia-treated (hypADSC-Exo) human ADSCs, and their pro-angiogenic capacity was evaluated in human umbilical vein endothelial cells (HUVECs) and a nude mouse model of subcutaneous fat grafting. Protein array was used to compare the exosome-derived proteins between nADSC-Exo and hypADSC-Exo.Results: Compared with the nADSC-Exo group and untreated control, hypADSC-Exo treatment significantly promoted proliferation, migration and tube-formation capability of HUVECs. Protein array revealed that the levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) and their receptors (VEGF-R2, VEGF-R3), and monocyte chemoattractant protein 2 (MCP-2), monocyte chemoattractant protein 4 (MCP-4) were significantly higher in the hypADSC-Exo than in the nADSC-Exo. In the nude mice model of fat grafting, immunofluorescence of CD31 showed that hypADSC-Exo dramatically improved neovascularization around the graft. Furthermore, compared with nADSC-Exo and control groups, cotransplantation of hypADSC-Exo significantly increased the protein expression of EGF, FGF, VEGF/VEGF-R, angiopoietin-1(Ang-1) and tyrosine kinase with immunoglobulin-like and EGF-like domains 1(Tie-1, an angiopoietin receptor) in the grafted tissue at 30 days after transplantation. Immunohistochemical analysis demonstrated that hypADSC-Exo treatment significantly increased VEGF-R expression in the grafted tissue.Conclusions: Exosomes from hypoxia-treated human ADSCs possess a higher capacity to enhance angiogenesis in fat grafting, at least partially, via regulating VEGF/VEGF-R signaling.