Human Glioblastoma-Derived Mesenchymal Stem Cell to Pericytes Transition and Angiogenic Capacity in Glioblastoma Microenvironment
Human Glioblastoma-Derived Mesenchymal Stem Cell to Pericytes Transition and Angiogenic Capacity in Glioblastoma Microenvironment
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DOI：
10.1159/000488429
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Fu, Peng
中科院分区：
文献类型：
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作者：
Yi, Dongye;Xiang, Wei;Fu, Peng
背景/目的：肿瘤血管的形成和维持是胶质母细胞瘤发展的关键事件。间充质干细胞（MSC）已被证明可以分化为周细胞，并有助于胶质瘤微环境中的新血管形成。此外，胶质母细胞瘤来源的间充质干细胞（gb-MSCs），由CD 90-MSCs和CD 90（+）MSCs组成，是在胶质瘤血管化中更活跃的MSCs亚群。然而，gb-MSCs的功能和胶质母细胞瘤微环境中的microRNA（miRNA）修饰尚未完全阐明。在这里，我们专注于gb-MSCs的周细胞分化潜力和gb-MSCs在新血管形成和胶质母细胞瘤生长过程中的miRNA修饰。研究方法：体外培养时，采用流式细胞仪检测gb-MSCs的表面标志，油红O染色、茜素红染色、阿辛蓝染色检测gb-MSCs的分化潜能，cck 8试验和伤口愈合试验检测gb-MSCs在不同条件培养液中的增殖和迁移情况，免疫荧光染色和western blot检测gb-MSCs向周细胞转化的情况，流式细胞仪检测gb-MSCs向周细胞转化的情况。通过管形成测定分析血管生成能力;通过ELISA测定不同上清液中的细胞因子水平。此外，从gb-MSC中分离RNA，并使用RAffy miRNA微阵列分析miRNA修饰。结果如下：我们发现，胶质母细胞瘤条件培养基增加gb-MSC增殖和迁移，并能够诱导gb-MSC分化为周细胞。胶质母细胞瘤分泌血管生成因子，在恶性胶质母细胞瘤条件培养液中培养的gb-MSCs形成更多的管状结构，这些细胞也粘附在Matrigel上由人脐静脉内皮细胞（HUVECs）形成的管状血管上，以维持体外肿瘤血管结构。在体外恶性胶质母细胞瘤条件培养基中培养的gb-MSCs中miRNA表达也被修饰。结论：这些结果为胶质母细胞瘤中MSCs亚群的功能效应提供了新的见解，并可能有助于开发实体瘤的新疗法。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: Tumor vascular formation and maintenance are crucial events in glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to differentiate into pericytes and contribute to neovascularization in the glioma microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb-MSCs), which consist of CD90-MSCs and CD90(+) MSCs, are a subpopulation of MSCs that are more active in glioma vascularization. However, the functions of gb-MSCs and the microRNA (miRNA) modifications in the glioblastoma microenvironment have not yet been fully elucidated. Here, we focus on the pericyte differentiation potential of gb-MSCs and miRNA modifications in gb-MSCs during new vascular formation and glioblastoma growth. Methods: In vitro, surface markers of gb-MSCs were detected by flow cytometry; the differentiation potential was evaluated by Oil Red O staining, Alizarin Red staining and Alcian blue staining; the proliferation and migration of gb-MSCs in different conditioned media were analyzed by the cck8 test and wound-healing assay, respectively; gb-MSC to pericyte transition was detected by immunofluorescence staining and western blot assay; angiogenetic capacity was analyzed by tube formation assay; and levels of cytokines in different supernatant were determined by ELISA. Additionally, RNA was isolated from gb-MSCs, and miRNA modifications were analyzed using the RAffymetrix miRNA microarray. Results: We showed that glioblastoma-conditioned medium increased gb-MSC proliferation and migration and was capable of inducing gb-MSC differentiation into pericytes. Glioblastoma secreted angiogenic factors and gb-MSCs incubated in malignant glioblastoma-conditioned medium formed more tube-like structures, and these cells also adhered to tube-like vessels formed by human umbilical vein endothelial cells (HUVECs) on Matrigel to maintain tumor vascular structure in vitro. miRNA expression were also modified in gb-MSCs cultured in malignant glioblastoma-conditioned medium in vitro. Conclusion: These results provide new insight into the functional effects of a subpopulation of MSCs in glioblastoma and may help in the development of novel therapies for solid tumors. (C) 2018 The Author(s) Published by S. Karger AG, Basel