表达血管内皮生长因子的骨骼肌细胞可诱导大鼠毛细血管形成并减轻心脏损伤。
Skeletal muscle cells expressing VEGF induce capillary formation and reduce cardiac injury in rats.
作者信息
Becker Claudia, Lacchini Silvia, Muotri Alysson Renato, da Silva Gustavo José Justo, Castelli Jussara Bianchi, Vassallo Paula F, Menck Carlos Frederico Martins, Krieger José Eduardo
机构信息
Heart Institute (InCor)-LIM-13, University of São Paulo Medical School, São Paulo, Brazil.
出版信息
Int J Cardiol. 2006 Nov 18;113(3):348-54. doi: 10.1016/j.ijcard.2005.11.060. Epub 2006 May 3.
BACKGROUND
We tested a preemptive combined cell/gene therapy strategy of skeletal myoblasts transfected with Ad(5)RSVVEGF-165 in an ischemia/reperfusion rat model to increase collateral blood flow to nonischemic heart tissue.
METHODS
Lewis rats were injected with placebo (Control), 10(6) skeletal myoblasts (SkM), or 10(6) skeletal myoblasts transfected with Ad(5)RSVVEGF-165 (SkM(+)) into the left ventricle 1week before ischemia. Left ventricle end-diastolic pressure, scar area, and capillary density were assessed 4weeks later.
RESULTS
Local expression of human vascular endothelial growth factor was accompanied by an increase in capillary density in the SkM(+) group compared with that in the SkM and Control groups (700+/-40 vs. 289+/-18 and 318+/-59capillaries/mm(2), respectively; p<0.05). After 3weeks, the myocardial scar area was reduced in SkM(+) vs. Control (5.3+/-0.4% and 14.8+/-1.6%, p<0.05), while injected cells alone (SkM) did not cause improvement compared with Control (11.8+/-2.1% vs. 14.8+/-1.6%, p>0.05). The decrease in the scar area in SkM(+) was accompanied by an increase in the capillary density compared with that in SkM and Control 30days after cell injection (1005+/-108 vs. 524+/-16 and 528+/-26capillaries/mm(2), respectively; p<0.05). The scar areas were discrete (5.3-14.8%) and left ventricle end-diastolic pressure in all groups were comparable (p>0.05).
CONCLUSIONS
The combined cell/gene therapy strategy of genetically modified myoblast cells expressing angiogenic factors injected into the myocardium induced capillary formation and prevented the extension and development of cardiac damage associated with ischemia/reperfusion in rats.
背景
我们在大鼠缺血/再灌注模型中测试了一种先发制人的联合细胞/基因治疗策略，即注射用腺病毒5型（Ad(5)）重组含人血管内皮生长因子165（RSVVEGF-165）转染的骨骼肌成肌细胞，以增加流向非缺血心脏组织的侧支血流。
方法
在缺血前1周，将Lewis大鼠分为三组，分别向左心室注射安慰剂（对照组）、10⁶个骨骼肌成肌细胞（SkM）或10⁶个用Ad(5)RSVVEGF-165转染的骨骼肌成肌细胞（SkM(+)）。4周后评估左心室舒张末期压力、瘢痕面积和毛细血管密度。
结果
与SkM组和对照组相比，SkM(+)组人血管内皮生长因子的局部表达伴随着毛细血管密度的增加（分别为700±40、289±18和318±59根毛细血管/mm²；p<0.05）。3周后，SkM(+)组的心肌瘢痕面积较对照组减小（分别为5.3±0.4%和14.8±1.6%，p<0.05），而单独注射细胞（SkM）与对照组相比未显示出改善（分别为11.8±2.1%和14.8±1.6%，p>0.05）。与SkM组和对照组相比，细胞注射30天后SkM(+)组瘢痕面积的减小伴随着毛细血管密度的增加（分别为1005±108、524±16和528±26根毛细血管/mm²；p<0.05）。瘢痕面积离散（5.3 - 14.8%），所有组的左心室舒张末期压力相当（p>0.05）。
结论
向心肌内注射表达血管生成因子的基因修饰成肌细胞的联合细胞/基因治疗策略可诱导毛细血管形成，并预防大鼠缺血/再灌注相关的心脏损伤的扩展和发展。
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