Enhanced Myocardial Angiogenesis by Gene Transfer With Transplanted Cells
Enhanced Myocardial Angiogenesis by Gene Transfer With Transplanted Cells
复制标题
通过移植细胞的基因转移增强心肌血管生成
作者：
T. Yau;K. Fung;R. Weisel;T. Fujii;Donald A. G. Mickle;Ren
背景-心肌细胞移植和血管生成基因转移的结合可能改善梗死后左心室(LV)的血流灌注。我们评价了转导血管内皮生长因子(VEGF)的心脏细胞移植到心肌瘢痕中的血管生成作用。方法和结果：将编码VEGF165和绿色荧光蛋白的真核表达载体导入供体大鼠心肌细胞。同基因成年大鼠接受LV冷冻损伤，形成跨壁瘢痕。3周后，将4×106个转染组(n=14)、未转染组(n=13)或培养液(n=16)植入瘢痕中心。5周后评价左心功能、定量组织学和局部血流量。血管内皮生长因子165转染组的心肌细胞产生的细胞内血管内皮生长因子是未转染组的6.1倍。心肌瘢痕中心高倍视野下的毛细血管密度对照组为1.10±0.02，未转染组为3.90±0.11，转染组为6.30±0.11(P=0.0002)。瘢痕周边区毛细血管密度对照组为1.90±0.03，未转染组为6.4±0.10，转染组为8.7±0.16(P=0.004)。瘢痕内局部血流量对照组为8.8±0.8%，未转染组为10.4±0.7%，转染组为17.6±1.2%(P=0.03与对照组，P=0.07与未转染组比较)。在研究的时间点，与转基因细胞一起移植的左心功能没有差异。结论：转导血管内皮生长因子的心脏细胞移植比未经修饰的细胞移植诱导更多的血管生成。基因转移和细胞移植相结合的治疗策略可能改善心肌梗死后的左心室血流灌注和功能。
Background—The combination of myocardial cell transplantation and angiogenic gene transfer may improve postinfarction left ventricular (LV) perfusion. We evaluated the angiogenic effect of heart cells transfected with vascular endothelial growth factor (VEGF) and transplanted into a myocardial scar. Methods and Results—Donor rat heart cells were transfected with plasmids encoding VEGF165 and green fluorescence protein. Syngeneic adult rats underwent LV cryoinjury to create a transmural scar. Three weeks later, 4×106 transfected heart cells (n=14), untransfected heart cells (n=13), or culture medium (n=16) were transplanted into the center of the scar. After 5 weeks, LV function, quantitative histology, and regional blood flow were evaluated. Plates of heart cells transfected with VEGF165 produced 6.1 times more intracellular VEGF than nontransfected cells. Capillary density (mean±SEM) per high-power field in the center of the myocardial scar was 1.1±0.02 in control rats, 3.9±0.11 in untransfected rats, and 6.3±0.11 in transfected rats (P =0.0002). Capillary density in the border zone around the scar was 1.9±0.03 in control rats, 6.4±0.10 in untransfected rats, and 8.7±0.16 in transfected rats (P =0.004). Regional blood flow within the scar was 8.8±0.8% of normalized flow in control hearts, 10.4±0.7% in hearts transplanted with untransfected cells, but 17.6±1.2% in hearts transplanted with transfected cells (P =0.03 versus control, P =0.07 versus nontransfected). There was no difference in LV function attributable to transplantation with transfected cells at the time point studied. Conclusions—Transplantation of heart cells transfected with VEGF induced greater angiogenesis than transplantation of unmodified cells. Combined gene transfer and cell transplantation strategies may improve postinfarction LV perfusion and function.
DOI：
10.1172/jci117627
发表时间：
1995
期刊：
The Journal of clinical investigation
影响因子：
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作者：
Gou Young Koh;Seong-Jin Kim;M. Klug;K. Park;K. Park;M. Soonpaa;Loren J. Field
通讯作者：
Gou Young Koh;Seong-Jin Kim;M. Klug;K. Park;K. Park;M. Soonpaa;Loren J. Field