[The experimental studies on cell transplantation into chronic ischemic myocardium using mesenchymal stem cells modified by recombinant adenovirus carrying vascular endothelial growth factors 165 gene].
OBJECTIVE
To observe the therapeutic effect of vascular endothelial growth factors 165 (VEGF165) gene expressing mesenchymal stem cells (MSCs) in chronic myocardial infarction model by providing enhanced cardioprotection, followed by angiogenic effects in infarcted myocardium.


METHODS
Recombinant adenovirus vector carrying VEGF165 gene (rAd-VFGF165) was constructed. MSCs were harvested through gradient centrifugation, then were cultivated, multiplied and expanded. Recombinant adenoviruses mediated VEGF165 gene were transfected into MSCs, and the MSCs were labelled by DAPI. The left anterior descending branch of rabbits were ligated to establish a myocardial infarction model; and the animals survived for 6 weeks were randomly divided into three groups: VEGF165-expressing MSCs transplanted (Group I), MSCs transplanted (Group II) and dulbecco modified eagles medium injected (Group III). At 4 weeks after cell transplantation, the MSCs were detected by DAPI staining in infarcted region. The cardiac functions were estimated by UCG. The microvascular density in infarcted area were estimated through CD34 immunohistochemical analysis.


RESULTS
Four weeks after cell transplantation, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in Group I compared with Group II and control group (P < 0.05). DAPI positive cells were most increased in Group I.


CONCLUSIONS
The transplantation of VEGF165-expressing MSCs had a better therapeutic effect than the transplantation of simplex MSCs. This combined strategy of MSCs transplantation with vgene therapy could be a useful therapy for the treatment of myocardial infarction.
Gao
Chang-qing
CQ
Department of Cardiovascular Surgery, General Hospital of People's Liberation Army, Beijing 100853, China. gaochq301@yahoo.com
Yang
Ming
M
Li
Li-bing
LB
Chen
Wei
W
Hou
Li-hua
LH
Li
Jian-min
JM
Li
Bing
B
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011817:Rabbits; D011897:Random Allocation; D014162:Transfection; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A