IL-8 enhances the angiogenic potential of human bone marrow mesenchymal stem cells by increasing vascular endothelial growth factor
IL-8 enhances the angiogenic potential of human bone marrow mesenchymal stem cells by increasing vascular endothelial growth factor
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DOI：
10.1002/cbin.10294
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发表时间：
2014-09-01
影响因子：
3.9
通讯作者：
Jeun, Sin-Soo
中科院分区：
文献类型：
--
作者：
Hou, Yun;Ryu, Chung Heon;Jeun, Sin-Soo
间充质干细胞（MSCs）的有益作用部分是通过旁分泌产生细胞保护因子和营养因子介导的。血管内皮生长因子（VEGF）作为旁分泌营养因子从MSC中释放，通过调节血管生成和促进损伤组织的血运重建来发挥干细胞的治疗作用。白细胞介素-8（IL-8）是一种具有强促血管生成特性的炎性趋化因子，在缺血性脑中上调，并已显示可促进骨髓源性细胞归巢至损伤部位。然而，IL-8对MSC旁分泌功能的影响仍然未知。我们发现IL-8诱导VEGF的产生和Akt和ERK的磷酸化。这两种作用都可以被抑制剂（LY 294002、PD 098059）或siRNA介导的人骨髓间充质干细胞（hBM-MSCs）中Akt和ERK沉默所阻断。与基础分泌的VEGF相比，hBM-MSC中IL-8诱导的VEGF产生显著增加了Matrigel上的管形成。在大鼠中风模型中，与单独hBM-MSC治疗相比，给予IL-8处理的hBM-MSC减少了缺血边界区的梗死体积并增加了血管生成。总之，IL-8部分地通过PI 3 K/Akt和MAPK/ERK信号转导途径刺激hBM-MSC中VEGF的产生，并且施用IL-8处理的hBM-MSC增加中风后的血管生成。这种方法可用于优化多种疾病的基于MSC的治疗，包括中风、心肌缺血和脊髓损伤。
The beneficial effects of mesenchymal stem cells (MSCs) are mediated partly by the paracrine production of cytoprotective and trophic factors. Vascular endothelial growth factor (VEGF) is released from MSCs as a paracrine trophic factor and contributes to the therapeutic effects of the stem cell by regulating angiogenesis and promoting revascularization in injured tissues. Interleukin-8 (IL-8), an inflammatory chemokine with potent proangiogenic properties, is upregulated in the ischemic brain and has been shown to promote homing of bone marrow-derived cells to injured sites. However, the effect of IL-8 on MSCs paracrine function remains unknown. We found that IL-8 induced VEGF production and phosphorylation of Akt and ERK. Both effects could be blocked by inhibitors (LY294002, PD098059) or siRNA-mediated silencing of Akt and ERK in human bone marrow MSCs (hBM-MSCs). IL-8-induced VEGF production in hBM-MSCs significantly increased tube formation on Matrigel compared with basal secreted VEGF. In a rat stroke model, administration of IL-8-treated hBM-MSCs decreased the infarction volume and increased angiogenesis in the ischemic boundary zone compared with hBM-MSC treatment alone. In conclusion, IL-8 stimulates VEGF production in hBM-MSCs in part via the PI3K/Akt and MAPK/ERK signal transduction pathways and that administration of IL-8-treated hBM-MSCs increases angiogenesis after stroke. This approach may be used to optimize MSC-based therapies for numerous diseases including stroke, myocardial ischemia, and spinal cord injury.