Therapeutic angiogenesis using basic fibroblast growth factor in combination with a collagen matrix in chronic hindlimb ischemia.

Therapeutic angiogenesis using basic fibroblast growth factor in combination with a collagen matrix in chronic hindlimb ischemia.
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DOI:
10.1100/2012/652794
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发表时间:
2012
影响因子:
--
通讯作者:
Wang X
Wang X
中科院分区:
其他
文献类型:
--
作者:
Zhou J;Zhao Y;Wang J;Zhang S;Liu Z;Zhen M;Liu Y;Liu P;Yin Z;Wang X

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虽然通过血管生成细胞因子的治疗性血管生成是改善缺血区域局部血流的可行策略,但需要建立最佳递送模式。在这里,我们设计了一个复合物的胶原基质(CM)和碱性成纤维细胞生长因子(bFGF),并评估其促血管生成作用在缺血后肢。使用冻干法制备bFGF-CM。观察了CM的形态、孔隙率和毒性。评价了bFGF的释放特性和释放的bFGF的生物活性。将bFGF-CM肌内植入兔缺血后肢模型。每隔一段时间测定缺血肢体氧饱和度参数(OSP),评价肢体血流灌注情况。组织学检查以评估血管生成水平。CM和bFGF-CM具有相同的多孔结构,无细胞毒性。释放曲线持续10天,释放的bFGF保持生物活性。2、4周时bFGF-CM组OSP明显高于CM组、bFGF组和缺血组。bFGF-CM组的毛细血管和成熟血管数量明显多于未处理对照组、CM组和bFGF组。因此,与不含bFGF的CM相比,bFGF-CM能够安全有效地长期释放bFGF,并改善缺血后肢中的血管生成。
Although therapeutic angiogenesis by angiogenic cytokines is a feasible strategy to improve regional blood flow in ischemic regions, the optimal delivery mode needs to be established. Here we designed a complex of collagen matrix (CM) and basic fibroblast growth factor (bFGF) and evaluated its proangiogenic effect in ischemic hindlimbs. The bFGF-CM was prepared using lyophilization. The morphology, porosity and toxicity of CM were examined. The bFGF releasing profile and bioactivity of released bFGF were assessed. bFGF-CM was intramuscularly implanted into the rabbit ischemic hindlimb model. Oxygen saturation parameters (OSP) of ischemic hindlimbs was measured to evaluate the extremity perfusion at intervals. Histological examination was performed to evaluate the level of angiogenesis. The CM and bFGF-CM were of identical multiporous structure lacking cytotoxicity. The releasing profile lasted 10 days and the released bFGF remained bioactive. OSP in bFGF-CM group was significantly higher than that in CM, bFGF and ischemic groups at 2 and 4 weeks. The number of capillaries and mature vessels in bFGF-CM group were significantly greater than that in untreated control, CM and bFGF groups. Therefore, bFGF-CM enables the safe and effective long-term release of bFGF with improved angiogenesis in ischemic hindlimbs compared with CM devoid of bFGF.
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