Shear Stress Induces Nitric Oxide-Mediated Vascular Endothelial Growth Factor Production in Human Adipose Tissue Mesenchymal Stem Cells
Shear Stress Induces Nitric Oxide-Mediated Vascular Endothelial Growth Factor Production in Human Adipose Tissue Mesenchymal Stem Cells
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DOI：
10.1089/scd.2009.0195
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Krieger, Jose Eduardo
中科院分区：
文献类型：
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作者：
Bassaneze, Vinicius;Barauna, Valerio Garrone;Krieger, Jose Eduardo
已经证明，人类脂肪组织来源的间充质干细胞（hASC）可增强缺血组织中的血管密度，表明它们可以分化为血管细胞或释放可能刺激新血管生成的血管生成因子。此外，有证据表明剪切应力（SS）可能会激活胚胎和内皮前体干细胞增殖和分化为内皮细胞（EC）。在这项工作中，我们研究了层流 SS 在促进 hASC 分化为 EC 方面的作用。通过 RT-PCR 和流式细胞术检测，由锥板系统产生的 SS（10 dyn/cm(2) 长达 96 小时）未能在 hASC 上诱导 EC 标记（CD31、vWF、Flk-1）。相比之下，一氧化氮（通过格里斯反应测定）和血管内皮生长因子（VEGF；通过ELISA）的累积产生长达96小时的SS刺激（nmol/10(4)细胞中的NO2-：静态：0.20 +/- 0.03；SS：1.78 +/- 0.38，n = 6；pg/10(4)细胞中的VEGF：静态： 191.31 +/- v35.29； SS：372.80 +/- 46.74，n = 6，P < 0.05）。有趣的是，5 mM N(G)-L-硝基精氨酸甲酯 (L-NAME) 处理消除了 VEGF 的产生（pg/10(4) 细胞中的 VEGF：SS：378.80 +/- 46.74，n = 6；SS + L-NAME：205.84 +/- 91.66，n = 4，P < 0.05）。结果表明，尽管 SS 在测试条件下未能诱导 hASC 中的 EC 表面标记，但它刺激了 NO 依赖性 VEGF 的产生。
It has been demonstrated that human adipose tissue-derived mesenchymal stem cells (hASCs) enhance vascular density in ischemic tissues, suggesting that they can differentiate into vascular cells or release angiogenic factors that may stimulate neoangiogenesis. Moreover, there is evidence that shear stress (SS) may activate proliferation and differentiation of embryonic and endothelial precursor stem cells into endothelial cells (ECs). In this work, we investigated the effect of laminar SS in promoting differentiation of hASCs into ECs. SS (10 dyn/cm(2) up to 96 h), produced by a cone plate system, failed to induce EC markers (CD31, vWF, Flk-1) on hASC assayed by RT-PCR and flow cytometry. In contrast, there was a cumulative production of nitric oxide (determined by Griess Reaction) and vascular endothelial growth factor (VEGF; by ELISA) up to 96 h of SS stimulation ( NO2- in nmol/10(4) cells: static: 0.20 +/- 0.03; SS: 1.78 +/- 0.38, n = 6; VEGF in pg/10(4) cells: static: 191.31 +/- v35.29; SS: 372.80 +/- 46.74, n = 6, P < 0.05). Interestingly, the VEGF production was abrogated by 5 mM N(G)-L-nitro-arginine methyl ester (L-NAME) treatment (VEGF in pg/10(4) cells: SS: 378.80 +/- 46.74, n = 6; SS + L-NAME: 205.84 +/- 91.66, n = 4, P < 0.05). The results indicate that even though SS failed to induce EC surface markers in hASC under the tested conditions, it stimulated NO-dependent VEGF production.