Insight into the proteomic profiling of exosomes secreted by human OM-MSCs reveals a new potential therapy
Insight into the proteomic profiling of exosomes secreted by human OM-MSCs reveals a new potential therapy
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对人类 OM-MSC 分泌的外泌体的蛋白质组学分析揭示了一种新的潜在疗法
DOI：
10.1016/j.biopha.2020.110584
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发表时间：
2020
影响因子：
7.5
通讯作者：
Ming Lu
中科院分区：
文献类型：
--
作者：
Chengfeng Xun;Lite Ge;Feng Tang;Lu Wang;Yi Zhuo;Lang Long;Jiaomei Qi;Li Hu;Da Duan;Ping Chen;Ming Lu
间充质基质细胞（Mesenchymal stromal cells，MSCs）已被用于治疗神经元损伤和神经退行性疾病。其潜在机制可能涉及旁分泌因子的分泌增加，从而促进组织修复。目前，外泌体已被认为是旁分泌和旁分泌因子的重要组成部分。MSC外泌体代表了开发新的无细胞治疗方法的有希望的机会。在这项研究中，使用超离心法提取并纯化来自鼻嗅粘膜MSC（OM-MSC）的外泌体，得到40-130 nm的外泌体直径。与其他外泌体类似，OM-MSC外泌体是CD 63-和CD 81-阳性和钙连接蛋白-阴性的。在功能上，OM-MSC exosomes促进人脑微血管内皮细胞（HBMEC）的增殖和迁移。本研究分析了OM-MSC外泌体旁分泌蛋白质组。通过LC-MS/MS共鉴定了304种外泌体相关蛋白，包括纤溶酶原激活物抑制剂1（SERPINE 1）、胰岛素样生长因子结合蛋白家族成员（IGFBP 4和5）、表皮生长因子受体（EGFR）、神经源性位点缺口同源蛋白2（NOTCH 2）、载脂蛋白E（APOE）和热休克蛋白HSP 90-β（HSP 90 AB 1）。已知这些分子在神经营养、血管生成、细胞生长、分化、凋亡和炎症中是重要的，并且与组织修复和神经恢复的机制高度相关。这些观察结果可能为进一步评估OM-MSC外泌体作为一种新型治疗方式的潜力提供基础。
Mesenchymal stromal cells (MSCs) have been used for the treatment of neuronal injury and neurodegenerative diseases. Their underlying mechanism may involve increased secretion of paracrine factors, which promotes tissue repair. Presently, exosomes have been regarded as important components of paracrine secretion and paracrine factors. MSC exosomes represent a promising opportunity to develop novel cell-free therapy approaches. In this study, exosomes from nasal olfactory mucosa MSCs (OM-MSCs) were extracted and purified using ultracentrifugation, resulting in exosome diameters of 40–130 nm. Similar to other exosomes, OM-MSC exosomes were CD63- and CD81-positive and calnexin-negative. Functionally, OM-MSC exosomes promoted human brain microvascular endothelial cell (HBMEC) proliferation and migration. The present study analyzed the OM-MSC exosome paracrine proteome. A total of 304 exosome-associated proteins were identified by LC–MS/MS, including plasminogen activator inhibitor 1 (SERPINE 1), insulin-like growth factor binding protein family members (IGFBP 4 and 5), epidermal growth factor receptor (EGFR), neurogenic locus notch homolog protein 2 (NOTCH 2), apolipoprotein E (APOE), and heat shock protein HSP90-beta (HSP90AB1). These molecules are known to be important in neurotrophic, angiogenesis, cell growth, differentiation, apoptosis, and inflammation and are highly correlated with the mechanism of tissue repair and neural restoration. These observations may provide a basis for further evaluation of OM-MSC exosome potential as a novel therapeutic modality.