Gene manipulated peritoneal cell patch repairs infarcted myocardium.
Gene manipulated peritoneal cell patch repairs infarcted myocardium.
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DOI：
10.1016/j.yjmcc.2009.10.032
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发表时间：
2010-04
影响因子：
5
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Huang W;Zhang D;Millard RW;Wang T;Zhao T;Fan GC;Ashraf A;Xu M;Ashraf M;Wang Y
开发了一种使用同源腹膜基质的基因操作细胞贴片，并在心肌梗死后应用于修复瘢痕心肌。我们使用腺病毒转导对雄性大鼠间充质干细胞（MSC）进行基因工程改造，使其过表达CXCR4/绿色荧光蛋白（GFP）（MSCCXCR4），或为空载体对照（MSCNull），或使用靶向CXCR4的小干扰RNA（MSCsiRNA）。通过实时定量聚合酶链反应（qPCR）和酶联免疫吸附测定（ELISA）研究基因表达。将细胞在切除的腹膜上培养9天。在雌性大鼠心脏左前降支（LAD）冠状动脉结扎2周后，将腹膜贴片细胞面朝下贴在瘢痕心肌上。通过绿色荧光蛋白阳性细胞的存在来确定植入效果。细胞植入1个月后，进行超声心动图检查，并摘取心脏进行组织学分析。测量左心室（LV）纤维化程度、左心室前壁厚度（AWT）以及移植物边缘的血管密度。与MSCNull组相比，在常氧条件下培养的MSCCXCR4组趋化因子显著上调，在缺氧暴露后进一步增加。在使用腹膜贴片进行细胞移植1个月后，在MSCCXCR4组梗死心肌内及其周围观察到大量绿色荧光蛋白阳性细胞。与MSCNull对照组的相同变量相比，MSCCXCR4组的左心室前壁厚度、左心室纤维化程度和左心室功能均显著改善。这些有益效果在MSCsiRNA组中不存在。基因操作的接种间充质干细胞的腹膜贴片促进组织营养（血管生成），减少心肌重塑，并增强心肌梗死后的心脏功能。
A gene manipulated cell patch using a homologous peritoneum substrate was developed and applied after myocardial infarction to repair scarred myocardium. We genetically engineered male rat mesenchymal stem cells (MSC) using adenoviral transduction to over-express CXCR4/green fluorescent protein (GFP) (MSCCXCR4) or MSCNull or siRNA targeting CXCR4 (MSCsiRNA). Gene expression was studied by real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). Cells were cultured on excised peritoneum for 9 days. Two weeks after left anterior descending (LAD) coronary artery ligation in female hearts, the peritoneum patch was applied over the scarred myocardium, cell side down. Efficacy of engraftment was determined by presence of GFP positive cells. One month after cell implantation, echocardiography was performed and hearts were harvested for histological analysis. Left ventricle (LV) fibrosis, LV anterior wall thickness (AWT) and blood vessel density at the margins of the graft were measured. There was significant up-regulation of the chemokines in the MSCCXCR4 group cultured under normoxic conditions when compared to the MSCNull group and a further increase was observed after exposure to hypoxia. One month after cell transplantation with the peritoneum patch, substantial numbers of GFP-positive cells were observed in and around the infarcted myocardium in MSCCXCR4 group. LV AWT, LV fibrosis and LV function were significantly improved in the MSCCXCR4 group as compared to these same variables in the MSCNull control. These salutary effects were absent in MSCsiRNA group. The gene manipulated MSC-seeded peritoneum patch promotes tissue nutrition (angiogenesis), reduces myocardial remodeling, and enhances heart function after myocardial infarction.
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影响因子：
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通讯作者：
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