CXCL8 enhances the angiogenic activity of umbilical cord blood-derived outgrowth endothelial cells in vitro
CXCL8 enhances the angiogenic activity of umbilical cord blood-derived outgrowth endothelial cells in vitro
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DOI：
10.1042/cbi20090225
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发表时间：
2011-03-01
影响因子：
3.9
通讯作者：
Sonoda, Yoshiaki
中科院分区：
文献类型：
--
作者：
Kimura, Takashi;Kohno, Hirao;Sonoda, Yoshiaki
OECs（生长内皮细胞），也称为晚期内皮祖细胞（晚期内皮祖细胞），除了体外管形成能力外，还具有高增殖潜力。在缺血性动物模型中，注射的OECs被整合到再生血管中并改善了新血管形成。先前的报道已经证明了CXCL 8的表达在缺血组织中上调。还已经证明CXCL 8刺激成熟EC（内皮细胞）的血管生成活性。因此，已经表明CXCL 8在缺血组织中的新血管形成中起重要作用。然而，CXCL 8是否也刺激OECs的血管生成活性仍不确定。本研究评价了CXCL 8对体外培养的嗅鞘细胞血管生成活性的影响。OEC从人UCB（脐带血）来源的单核细胞中分离。OECs的表型通过流式细胞术、免疫染色和实时AT（逆转录）-PCR进行评估。通过迁移实验和基质胶毛细管形成实验观察CXCL 8对OECs的影响。从脐带血中分离的OEC克隆表达OEC表型。此外，CXCL 8受体（CXCR 1和CXCR 2）在这些OEC克隆上表达。CXCL 8可显著促进OECs的跨孔迁移和毛细血管形成。抗CXCR 2中和抗体可阻断CXCL 8诱导的嗅鞘细胞跨孔迁移，提示CXCL 8/CXCR 2轴参与跨孔迁移。这些结果表明，CXCL 8刺激体外UCB衍生的OEC的血管生成活性。
OECs (outgrowth endothelial cells), also known as late-EPCs (late-endothelial progenitor cells), have a high proliferation potential in addition to in vitro tube formation capability. In ischaemic animal models, injected OECs were integrated into regenerating blood vessels and improved neovascularization. Previous reports have demonstrated the expression of CXCL8 to be up-regulated in ischaemic tissues. It has also been documented that CXCL8 stimulates the angiogenic activity of mature ECs (endothelial cells). Therefore, it has been suggested that CXCL8 plays an important role in neovascularization in ischaemic tissues. However, it is still uncertain whether CXCL8 also stimulates the angiogenic activity of OECs. This study evaluated the effects of CXCL8 on the angiogenic activity of OECs in vitro. OECs were isolated from human UCB (umbilical cord blood)-derived mononuclear cells. Phenotypes of the OECs were assessed by flow cytometry, immunostaining, and real-time AT (reverse transcription)-PCR. The effects of CXCL8 on OECs were investigated by transwell migration assay and capillary tube formation assay on Matrigel. The OEC clones isolated from UCB expressed OEC phenotypes. In addition, CXCL8 receptors (CXCR1 and CXCR2) were expressed on these OEC clones. CXCL8 significantly stimulated the transwell migration and capillary tube formation of OECs. Neutralizing antibody against CXCR2, but not CXCR1, abolished a transwell migration of OECs induced by CXCL8, suggesting the involvement of CXCL8/CXCR2 axis in transwell migration. These results demonstrate that CXCL8 stimulates the angiogenic activity of UCB-derived OECs in vitro.