Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor
Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor
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DOI：
10.1007/s00109-004-0546-z
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发表时间：
2004-08-01
影响因子：
4.7
通讯作者：
Sim, EKW
中科院分区：
文献类型：
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作者：
Haider, HK;Ye, L;Sim, EKW
本研究探讨了携带人血管内皮细胞生长因子(165)的人骨骼肌成肌细胞用于心脏修复的血管肌肉生成的可能性。采用冠状动脉结扎法建立18头雌性猪慢性心肌梗死模型。实验动物随机分为：注射DMEM组(6只)、移植成肌细胞组(5只)和移植VEGF165成肌细胞组(7只)。3周后，第2、3组大鼠左室心肌内注射含3x10(8)成肌细胞的DMEM 5ml心肌内注射，I组注射无细胞DMEM 5ml。每天给予环孢素5 mg/kg，连续6周。用荧光微球测量局部血流量。在移植后6-12周内移植心脏进行组织学研究。组织学检查显示表达Lac-Z的成肌细胞在宿主组织中存活。低倍视野(X100)时，第3组的毛细血管密度为57.13+/-4.20，明显高于其他各组。移植后6周和12周，移植组局部血流量明显改善，分别为2.41±0.11和3.39±0.11 ml(-1)min(-1)g(-1)；左心室射血分数从移植后6周的31.25±-4.09%增加到移植后6周的43.0+/-2.68%。
This study investigated the potential of human skeletal myoblast carrying human VEGF(165) for angiomyogenesis for cardiac repair. A porcine heart model of chronic infarction was created in 18 female swine by coronary artery ligation. The animals were randomized into: group 1, DMEM injected (n=6), group 2, myoblast transplanted (n=5) and group 3, VEGF165 myoblast transplanted (n=7). Three weeks later 5 ml DMEM containing 3x10(8) myoblast carrying exogenous genes were injected into 20 sites in left ventricle intramyocardially in groups 2 and 3. Group I animals were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted between 6-12 weeks after transplantation for histological studies. Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density at low power field (x100) was 57.13+/-4.20 in group 3 which was significantly higher than the other groups. Regional blood flow was significantly improved 6 and 12 weeks after transplantation, which was 2.41+/-0.11 and 3.39+/- 0.11 ml(-1) min(-1) g(-1)), respectively, in group 3. Left ventricular ejection fraction increased from 31.25+/-4.09% to 43.0+/-2.68% at 6 weeks in group 3. Human myoblasts are potential transgene carriers for the myocardium, in addition to strengthening the weakened myocardium through myogenesis.