Hypoxic Preconditioning Enhances Cellular Viability and Pro-angiogenic Paracrine Activity: The Roles of VEGF-A and SDF-1a in Rat Adipose Stem Cells.
Hypoxic Preconditioning Enhances Cellular Viability and Pro-angiogenic Paracrine Activity: The Roles of VEGF-A and SDF-1a in Rat Adipose Stem Cells.
复制标题
缺氧预处理增强细胞活力和促血管生成旁分泌活性：VEGF-A 和 SDF-1a 在大鼠脂肪干细胞中的作用。
DOI：
10.3389/fcell.2020.580131
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发表时间：
2020
影响因子：
5.5
通讯作者：
Lu MJ
中科院分区：
文献类型：
--
作者：
Zhao Y;Zhang M;Lu GL;Huang BX;Wang DW;Shao Y;Lu MJ
为了实现体内植入的脂肪干细胞（ASC）的全部治疗潜力，提高干细胞的活力和促血管生成特性至关重要。在此，我们首先使用体外氧-葡萄糖剥夺（OGD）模型模拟缺血和缺氧条件，并证实ASC的低氧预处理可以提供改善的对OGD的保护并增强ASC的活力。其次，我们评估了低氧预处理对ASCs促血管生成潜力的影响，特别关注血管内皮生长因子-A（VEGF-A）和基质衍生因子-1a（SDF-1a）旁分泌活性在介导血管生成中的作用。我们通过一系列体内和体外血管生成实验模型发现，低氧预处理的ASCCM通过上调VEGF-A和SDF-1a的表达以及二者之间的协同作用而促进血管生成。最后，为了探讨VEGF/VEGFR 2和SDF-1a/CXCR 4轴驱动血管生成的可能下游机制，我们评估了参与血管生成信号转导通路的相关蛋白激酶，并显示VEGF/VEGFR 2和SDF-1a/CXCR 4轴可能通过激活Akt协同促进血管生成。总的来说，我们的研究结果表明，低氧预处理可能构成一个有前途的策略，以提高细胞活力和血管生成的移植ASCs，从而提高成功率的干细胞为基础的治疗在组织工程。
To achieve the full therapeutic potential of implanted adipose stem cells (ASCs) in vivo, it is crucial to improve the viability and pro-angiogenic properties of the stem cells. Here, we first simulated the conditions of ischemia and hypoxia using the in vitro oxygen-glucose deprivation (OGD) model and confirmed that hypoxic preconditioning of ASCs could provide improved protection against OGD and enhance ASC viability. Second, we assessed the effect of hypoxic preconditioning on pro-angiogenic potential of ASCs, with a particular focus on the role of vascular endothelial growth factor-A (VEGF-A) and stromal derived factor-1a (SDF-1a) paracrine activity in mediating angiogenesis. We found that the conditioned medium of ASCs (ASCCM) with hypoxic preconditioning enhanced angiogenesis by a series of angiogenesis assay models in vivo and in vitro through the upregulation of and a synergistic effect between VEGF-A and SDF-1a. Finally, to investigate the possible downstream mechanisms of VEGF/VEGFR2 and SDF-1a/CXCR4 axes-driven angiogenesis, we evaluated relevant protein kinases involved the signal transduction pathway of angiogenesis and showed that VEGF/VEGFR2 and SDF-1a/CXCR4 axes may synergistically promote angiogenesis by activating Akt. Collectively, our findings demonstrate that hypoxic preconditioning may constitute a promising strategy to enhance cellular viability and angiogenesis of transplanted ASCs, therein improving the success rate of stem cell-based therapies in tissue engineering.