Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limb ischemia

Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limb ischemia
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DOI:
10.1517/14712598.8.6.705
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发表时间:
2008-05
影响因子:
4.6
通讯作者:
Yoshihito Tachi;D. Fukui;Y. Wada;Megumi Koshikawa;S. Shimodaira;Uichi Ikeda;J. Amano
Yoshihito Tachi;D. Fukui;Y. Wada;Megumi Koshikawa;S. Shimodaira;Uichi Ikeda;J. Amano
中科院分区:
医学3区
文献类型:
--
作者:
Yoshihito Tachi;D. Fukui;Y. Wada;Megumi Koshikawa;S. Shimodaira;Uichi Ikeda;J. Amano

文献摘要

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目的:骨髓单个核细胞(BM-MNC)移植(BMI)治疗重症肢体缺血,尤其是Buerger病,临床效果良好,但其作用机制尚不清楚。在这项研究中,我们调查了BMI治疗后血清血管生成相关因子水平的变化。研究设计/方法:从19例患者中筛选出12例BMI治疗非常有效的患者,其中9例为Buerger病,2例为动脉硬化闭塞症,1例为系统性硬化症。静脉血来源于患者受肢的股静脉或肱静脉。结果如下:BMI治疗后24 h血清肾上腺髓质素(AM)、可溶性血管细胞粘附分子-1(sVCAM-1)和C反应蛋白(CRP)水平较BMI治疗前显著升高(p < 0.05)。BMI治疗后1周至3个月,血清血管内皮生长因子(VEGF)水平显著升高(p < 0.05)。BMI治疗2周后血清NO水平显著升高(p < 0.05)。植入的细胞数量与BMI治疗后显著增加的测量的血管生成相关因子的血清水平之间没有相关性。结论:BMI治疗的机制包括早期和晚期。早期涉及植入细胞的直接作用,晚期涉及间接的旁分泌作用。此外,当我们植入足够水平的骨髓(600 ml)治疗严重肢体缺血时,BMI治疗被认为是有效的。
Objective: Bone marrow mononuclear cell (BM-MNC) implantation (BMI) for critical severe limb ischemia especially for Buerger's disease shows excellent clinical results but the mechanism of this treatment is still unknown. In this study, we investigated the changes in serum levels of angiogenesis-related factors after BMI treatment. Research design/methods: Twelve patients whose BMI treatments were clinically very effective was selected out of ninteen cases, nine patients had Buerger's disease, two patients had arteriosclerosis obliterans and one had systemic sclerosis. Venous bood from femoral vein or brachial vein of the recipient limbs of these patients. Results: Adrenomedulin (AM), soluble vascular cell adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) serum levels 24 h after BMI treatment were significantly increased compared with those before BMI treatment (p < 0.05). Vascular endothelial growth factor (VEGF) serum levels after BMI treatment significantly increased between 1 week and 3 months after BMI treatment (p < 0.05). Nitric oxide (NO) serum levels after BMI treatment increased significantly 2 weeks after BMI treatment (p < 0.05). There was no correlation between the numbers of implanted cells and serum levels of measured angiogenesis-related factors that were significantly increased after BMI treatment. Conclusion: It was concluded that the mechanism underlying BMI treatment consists of early and late phases. The early phase involves the direct action by implanted cells, and the late phase involves indirect paracrine action. In addition, it was considered that BMI treatment is effective when we implant a sufficient level of bone marrow (600 ml) to treat severe limb ischemia.