机构地区:[1]苏州大学附属第三医院血管外科,江苏省常州市213003 [2]复旦大学附属中山医院血管外科,上海市200032
出 处:《中国组织工程研究》2014年第20期3158-3164,共7页Chinese Journal of Tissue Engineering Research
摘 要:背景:动脉硬化性疾病的发病基础是内皮功能失调,循环中的内皮祖细胞数量和功能均下降,自身血管新生能力不足,单纯干细胞移植的疗效尚不确实,应用细胞因子以及基因修饰干细胞等方法是重要的研究方向。目的:观察基质细胞衍化因子1对内皮祖细胞移植促血管新生的影响。方法:制备20只单侧后肢缺血裸鼠模型,随机分为4组,分别给予静脉注射内皮祖细胞和肌肉注射基质细胞衍化因子1、静脉注射内皮祖细胞、局部肌肉注射基质细胞衍化因子1、肌肉注射培养液。造模后观察动物缺血后肢的皮温及存活情况,检测毛细血管/肌纤维比值、CD31和内皮型一氧化氮合酶表达情况。结果与结论:荧光标记内皮祖细胞移植后整合至缺血后肢肌肉。20只裸鼠死亡2只。联合治疗组、内皮祖细胞组、基质细胞衍化因子1组和空白对照组患肢保存率分别为80%,75%,20%和0。毛细血管/肌纤维比值检测结果显示,联合治疗组和内皮祖细胞组高于空白对照组(P<0.01),联合治疗组高于内皮祖细胞组、内皮祖细胞组高于基质细胞衍化因子1组(P<0.05)。血管密度检测结果显示,联合治疗组、内皮祖细胞组大于空白对照组(P<0.01),基质细胞衍化因子1组大于空白对照组(P<0.05),联合治疗组大于内皮祖细胞组、内皮祖细胞组大于基质细胞衍化因子1组(P<0.05)。联合治疗组和内皮祖细胞组缺血肌肉内皮型一氧化氮合酶阳性率分别为73.33%和53.33%(P>0.05)。提示内皮祖细胞可定向迁移至缺血组织,内皮祖细胞移植能促进治疗性血管新生,基质细胞衍化因子1可增强这一作用,内皮型一氧化氮合酶参与了内皮祖细胞促血管新生的过程。BACKGROUND:The endothelial dysfunction is the pathogenesis of arteriosclerotic disease, the quantity and function of endothelial progenitor cells are decreased within the cycle, leading to a poor capacity of neovascularizatio, the efficacy of stem celltransplantation alone is unclear, the combination of cytokines and gene-modified stem cells is the hotspot. OBJECTIVE:To observe the effect of stromal cel-derived factor-1 on the neovascularization after endothelial progenitor cells transplantation. METHODS:Unilateral hindlimb ischemia model was established in 20 athymic nude mice, and the mice were randomly divided into four groups:combined group (intravenous endothelial progenitor cells+intramuscular stromal cel-derived factor-1), endothelial progenitor cells group (intravenous injection of endothelial progenitor cells), stromal cel-derived factor-1 group (intramuscular injection of stromal cel-derived factor-1), and blank control group (intramuscular M199). The skin temperature of ischemic hindlimbs and survival of animals after transplantation were observed. The ratio of capil ary/skeletal muscle fiber was counted. The expression of CD31 and endothelial nitric oxide synthase were detected. RESULTS AND CONCLUSION:The fluorescence-labeled endothelial cells were embedded in ischemic hindlimb muscles after celltransplantation. Of the 20 nude mice, two mice died. The rate of ischemic hindlimb reserving was respectively 80%, 75%, 20%and 0 in combined group, endothelial progenitor cells group, stromal cel-derived factor-1 group, and blank control group. The capil ary/muscle fiber ratio in combined group and endothelial progenitor cells group was higher than that of blank control group (P0.05). Endothelial progenitor cells can migrate to ischemic tissues, endothelial progenitor cells transplantation can promote neovascularization, and stromal cel-derived factor-1 augments the neovascularization after celltransplantation, in which endothelial nitric oxide synthase is involved.
关 键 词:组织构建 组织工程 内皮细胞 内皮祖细胞 基质细胞衍化因子1 血管新生 细胞移植 缺血
分 类 号:R318[医药卫生—生物医学工程]
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