Improved angiogenic potency by implantation of ex vivo hypoxia prestimulated bone marrow cells in rats
Improved angiogenic potency by implantation of ex vivo hypoxia prestimulated bone marrow cells in rats
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DOI：
10.1152/ajpheart.00261.2002
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发表时间：
2002-08-01
影响因子：
4.8
通讯作者：
Matsuzaki, M
中科院分区：
文献类型：
--
作者：
Li, TS;Hamano, K;Matsuzaki, M
治疗性血管生成可以通过骨髓细胞的局部植入来诱导。我们试图通过在植入前对骨髓细胞进行体外缺氧刺激来增强这种治疗的血管生成潜力。收集骨髓细胞，并在33 ℃、2%O-2- 5%CO2 - 90%N-2（缺氧）或95%空气-5%CO2（常氧）条件下培养。培养24小时后，将细胞注射到大鼠缺血后肢中。低氧培养增加了骨髓细胞中血管内皮生长因子（VEGF）、血管内皮（VE）-钙粘蛋白和胎肝激酶-1（Flk-1）的mRNA表达，从2.5倍增加到5倍。缺氧培养的细胞移植后1天和3天，缺血后肢中VEGF蛋白的水平显著高于常氧培养或未培养的细胞。移植后2周，缺氧培养细胞组（89.7 +/- 5.5%）的微血管密度和血流速度也显著高于常氧培养细胞组（67.0 +/- 9.6%）或非培养细胞组（70.4 +/- 7.7%）（P < 0.001）。体外低氧刺激增加了骨髓细胞的VEGF mRNA表达和内皮分化，这两者共同有助于改善植入后缺血后肢的治疗性血管生成。
Therapeutic angiogenesis can be induced by local implantation of bone marrow cells. We tried to enhance the angiogenic potential of this treatment by ex vivo hypoxia stimulation of bone marrow cells before implantation. Bone marrow cells were collected and cultured at 33degreesC under 2% O-2-5% CO2-90% N-2 (hypoxia) or 95% air-5% CO2 (normoxia). Cells were also injected into the ischemic hindlimb of rats after 24 h of culture. Hypoxia culture increased the mRNA expression of vascular endothelial growth factor (VEGF), vascular endothelial (VE)-cadherin, and fetal liver kinase-1 (Flk-1) from 2.5-to fivefold in bone marrow cells. The levels of VEGF protein in the ischemic hindlimb were significantly higher 1 and 3 days after implantation with hypoxia-cultured cells than with normoxia-cultured or noncultured cells. The microvessel density and blood flow rate in the ischemic hind-limbs were also significantly (P < 0.001) higher 2 wk after implantation with hypoxia-cultured cells (89.7 +/- 5.5%) than with normoxia-cultured cells (67.0 +/- 9.6%) or noncultured cells (70.4 +/- 7.7%). Ex vivo hypoxia stimulation increased the VEGF mRNA expression and endothelial differentiation of bone marrow cells, which together contributed to improved therapeutic angiogenesis in the ischemic hindlimb after implantation.