Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model.

Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model.
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DOI:
10.1371/journal.pone.0067739
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Higashi Y
Higashi Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mikami S;Nakashima A;Nakagawa K;Maruhashi T;Iwamoto Y;Kajikawa M;Matsumoto T;Kihara Y;Chayama K;Noma K;Ochi M;Nishimura M;Tsuji K;Kato Y;Goto C;Higashi Y

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本研究的目的是确定自体间充质干细胞(MSCs)植入是否改善兔缺血肢体模型的内皮功能障碍。我们评估了MSC植入对肢体血流(LBF)对乙酰胆碱(ACh)(一种内皮依赖性血管扩张剂)和硝普钠(SNP)(一种内皮非依赖性血管扩张剂)的反应的影响,在患有肢体缺血的兔中,植入培养的MSC(n = 20)或注射生理盐水作为对照组(n = 20)。    使用电磁流量计测量LBF。共106间充质干细胞植入到每个缺血肢体。缺血肌肉的组织学切片显示,MSC植入组的毛细血管指数(毛细血管/肌纤维)大于对照组。激光多普勒血流灌注指数在MSC植入组较对照组显著增加。MSC组LBF对ACh的反应大于对照组。注射一氧化氮合酶抑制剂NG-硝基-L-精氨酸后,MSC植入组和对照组对ACh的LBF反应相似。SNP的扩血管作用在两组中相似。这些结果表明,MSC植入诱导血管生成和增强内皮依赖性血管舒张在兔缺血模型通过增加一氧化氮的生产。
The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a rabbit ischemic limb model. We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20) or saline was injected as a control group (n = 20). LBF was measured using an electromagnetic flowmeter. A total of 106 MSCs were implanted into each ischemic limb. Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber) was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.
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