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CCN1增强大鼠后肢缺血模型中骨髓移植的血管生成能力。

CCN1 enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia.

作者信息

Yin Cunping, Liang Yuan, Guo Shuguang, Zhou Xingli, Pan Xinghua

机构信息

Department of Vascular Surgery, Kunming General Hospital, Chengdu Military Command, Kunming, 650032, People's Republic of China,

出版信息

Mol Biol Rep. 2014 Sep;41(9):5813-8. doi: 10.1007/s11033-014-3455-4. Epub 2014 Jun 29.

DOI:10.1007/s11033-014-3455-4
PMID:24973877
Abstract

Implantation of autologous bone marrow mononuclear cells (BM-MNCs) has been performed in ischemic tissues, for stimulation of angiogenesis, but the limited number of BM-MNCs in patients with hindlimb ischemia disease may offset their overall therapeutic efficacy. CCN1 is a novel and essential regulator during angiogenesis. We evaluated whether CCN1 and BM-MNC are capable of promoting angiogenesis in hindlimb ischemia. In this study, we created the rat model of hindlimb ischemia, and then the rats were randomly divided into four groups: CCN1 infusion plus BM-MNC transplantation (CCN1 + BM-MNCs group), CCN1 infusion plus PBS injection (CCN1 group), vehicle infusion plus BM-MNC transplantation (BM-MNCs group) and vehicle infusion plus PBS injection (control group). The combination of CCN1 and BM-MNC therapy could increase blood perfusion, capillary/muscle fiber ratio and tissue oxygenation in ischemic hindlimb. Moreover, CCN1 could not only inhibit the apoptosis of BM-MNCs, but also enhance the adhesiveness of BM-MNCs to HUVEC. Taken together, CCN1 enhanced angiogenesis of BM-MNC transplantation, and combining CCN1 with BM-MNC transplantation is a useful alternative for ischemic limbs.

摘要

自体骨髓单个核细胞(BM-MNCs)已被植入缺血组织以刺激血管生成,但后肢缺血疾病患者体内BM-MNCs数量有限可能会抵消其整体治疗效果。CCN1是血管生成过程中的一种新型且重要的调节因子。我们评估了CCN1和BM-MNC是否能够促进后肢缺血中的血管生成。在本研究中,我们建立了大鼠后肢缺血模型,然后将大鼠随机分为四组:CCN1输注加BM-MNC移植组(CCN1 + BM-MNCs组)、CCN1输注加PBS注射组(CCN1组)、载体输注加BM-MNC移植组(BM-MNCs组)和载体输注加PBS注射组(对照组)。CCN1与BM-MNC联合治疗可增加缺血后肢的血液灌注、毛细血管/肌纤维比率和组织氧合。此外,CCN1不仅可以抑制BM-MNCs的凋亡,还能增强BM-MNCs与HUVEC的黏附性。综上所述,CCN1增强了BM-MNC移植的血管生成作用,将CCN1与BM-MNC移植相结合是治疗缺血肢体的一种有效替代方法。

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Angiogenic potential of BM MSCs derived from patients with critical leg ischemia.来自严重下肢缺血患者的骨髓间充质干细胞的血管生成潜力。
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VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting.
VEGF 对于缺氧诱导因子介导的血管生成是必不可少的,但对于血管内皮出芽是可有可无的。
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Autologous bone-marrow mononuclear cell implantation reduces long-term major amputation risk in patients with critical limb ischemia: a comparison of atherosclerotic peripheral arterial disease and Buerger disease.自体骨髓单核细胞移植可降低肢体缺血患者的长期大截肢风险:动脉粥样硬化性外周动脉疾病与伯格病的比较。
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Circulation. 2010 Dec 21;122(25):2688-98. doi: 10.1161/CIRCULATIONAHA.110.945261. Epub 2010 Dec 6.
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