Angiogenic and Immunomodulatory Properties of Endothelial and Mesenchymal Stem Cells.
Angiogenic and Immunomodulatory Properties of Endothelial and Mesenchymal Stem Cells.
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内皮和间质干细胞的血管生成和免疫调节特性。
DOI：
10.1089/ten.tea.2015.0316
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发表时间：
2016-02
影响因子：
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通讯作者：
Mustafa K
中科院分区：
文献类型：
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作者：
Bartaula-Brevik S;Pedersen TO;Finne-Wistrand A;Bolstad AI;Mustafa K
已经表明，当选择合适的细胞类型用于组织再生时，植入细胞对局部环境的影响是重要的。我们的目的是比较移植的人间充质干细胞（MSC）和人脐静脉内皮细胞（EC）的局部组织反应。MSC和EC在生物反应器系统中在聚（1-丙交酯-co-1，5-二氧杂环庚烷-2-酮）支架中培养1周，之后将其皮下植入NOD/SCID小鼠。3周后，取出支架，通过实时逆转录聚合酶链反应检测参与缺氧和炎症的选定基因的mRNA表达，并与相应蛋白的免疫荧光染色相关联。Toll样受体信号通路通过超阵列杂交检测。采用蛋白质组分析仪血管生成抗体芯片检测53种血管生成相关蛋白的表达。使用CD 31免疫组织化学定量血管化。缺氧诱导因子和血管生成的生物标志物的表达更强烈的上调，在植入EC比MSC，表明EC之间的低氧张力更高的敏感性。与MSC相比，EC植入后的低血糖信号增加，导致延长的急性炎症期，促进血管细胞的向内生长和循环的建立。在两个实验组中，炎症细胞因子在基因和蛋白质水平上的表达也不同，导致急性和慢性炎症细胞的募集发生改变。这些差异的最终结果是EC组中结构内血管形成增加。
It has been suggested that the effect of implanted cells on the local environment is important when selecting the appropriate cell type for tissue regeneration. Our aim was to compare the local tissue response to implanted human mesenchymal stem cells (MSC) and human umbilical vein endothelial cells (EC). MSC and EC were cultured in poly(l-lactide-co-1,5-dioxepan-2-one) scaffolds for 1 week in a bioreactor system, after which they were implanted subcutaneously in NOD/SCID mice. After 3 weeks, scaffolds were retrieved, and the mRNA expression of selected genes involved in hypoxia and inflammation was examined by real-time reverse transcription polymerase chain reaction and correlated with immunofluorescent staining for corresponding proteins. The Toll-like receptor signaling pathway was examined by superarray hybridization. The expression of 53 angiogenesis-related proteins was investigated by a proteome profiler angiogenesis antibody array kit. Vascularization was quantified using immunohistochemistry for CD31. The expression of hypoxia-inducible factors and biomarkers for angiogenesis was more strongly upregulated in response to implanted EC than to MSC, suggesting a higher sensitivity to low oxygen tension among EC. Hypoxic signaling was increased after implantation of EC compared with MSC, leading to a prolonged acute inflammatory phase that promoted ingrowth of vascular cells and establishment of the circulation. Inflammatory cytokines were also differently expressed at the gene and protein levels in the two experimental groups, resulting in altered recruitment of acute and chronic inflammatory cells. The end result of these differences was increased vessel formation within the constructs in the EC group.