Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia
Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia
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DOI：
10.1016/j.cardiores.2005.02.006
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发表时间：
2005-06-01
影响因子：
10.8
通讯作者：
Kitamura, S
中科院分区：
文献类型：
--
作者：
Iwase, T;Nagaya, N;Kitamura, S
目的：间充质干细胞（MSC）是一种多能细胞，可分化为多种细胞，包括内皮细胞和血管平滑肌细胞。虽然骨髓来源的单核细胞（MNC）的移植已经被应用于治疗严重的肢体缺血，很少有关于MSC和MNC之间的血管生成能力的比较信息。因此，我们注射同等数量的MSC或MNC在大鼠后肢缺血模型，并比较其治疗potential.Methods和结果：后立即创建后肢缺血，大鼠随机接受MSC移植（MSC组），MNC移植（MNC组），或车辆输注（对照组）。移植后3周，MNC组的激光多普勒灌注指数显著高于对照组（0.69 ± 0.1 vs. 0.57 ± 0.06，P < 0.01）。此外，MSC组的血液灌注有显著改善（0.81 +/- 0.08）。毛细血管密度在MSC组中最高。MSC组移植的细胞来源的内皮细胞的数量高于MNC组。仅在MSC组中检测到移植细胞来源的血管平滑肌细胞。在体外，MSC更耐受凋亡刺激（血清饥饿和缺氧）比MNC。结论：MSC移植引起的后肢缺血比MNC移植显着更大的改善。与MNC相比，MSC在缺血环境下存活良好，不仅分化为内皮细胞，而且分化为血管平滑肌细胞。因此，骨髓间充质干细胞移植可能是治疗严重外周血管疾病的一种新的治疗策略。(c)2005年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Mesenchymal stem cells (MSC) are pluripotent cells that differentiate into a variety of cells including endothelial cells and vascular smooth muscle cells. Although transplantation of bone marrow-derived mononuclear cells (MNC) has already been applied for the treatment of critical limb ischemia, little information is available regarding comparison of the angiogenic potency between MSC and MNC. Accordingly, we injected equal numbers of MSC or MNC in a rat model of hindlimb ischemia and compared their therapeutic potential.Methods and results: Immediately after creating hindlimb ischemia, rats were randomized to receive MSC transplantation (MSC group), MNC transplantation (MNC group), or vehicle infusion (Control group). Three weeks after transplantation, the laser Doppler perfusion index was significantly higher in the MNC group than in the Control group (0.69 +/- 0.1 vs. 0.57 +/- 0.06, P < 0.01). Furthermore, there was a marked improvement in blood perfusion in the MSC group (0.81 +/- 0.08). Capillary density was highest in the MSC group. The number of transplanted cell-derived endothelial cells was higher in the MSC group than in the MNC group. Transplanted cell-derived vascular smooth muscle cells were detected only in the MSC group. In vitro, MSC were more tolerant to apoptotic stimulus (serum starvation and hypoxia) than MNC.Conclusions: MSC transplantation caused significantly greater improvement in hindlimb ischemia than MNC transplantation. Compared with MNC, MSC survived well under an ischemic environment, and differentiated into not only endothelial cells but also vascular smooth muscle cells. Thus, MSC transplantation may be a new therapeutic strategy for the treatment of severe peripheral vascular disease. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.