Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat model of acute myocardial infarction.
We used human angiopoietin-1 (hAng1)-modified mesenchymal stem cells (MSCs) to treat acute myocardial infarction (AMI) in rats. The hAng1 gene was transfected into cultured rat MSCs using an adenoviral vector. Five million hAng-transfected MSCs (MSC(Ang1)) or green fluorescent protein transfected MSCs (MSC(GFP)) or PBS only (PBS group) were injected intramyocardially into the inbred Lewis rat hearts immediately after myocardial infarction. MSC(Ang1) survived in the infarcted myocardium, and expressed hAng1 at both mRNA and protein levels. The vascular density was higher in the MSC(Ang1) and MSC(GFP) groups than in the PBS group. The measurements of infarcted ventricular wall thickness, infarction area, and left ventricular diameter indicated that heart remodeling was inhibited and heart function was improved in both the MSC(Ang1) and MSC(GFP) groups. However, in contrast to the MSC(GFP) group, the MSC(Ang1) group showed enhanced angiogenesis and arteriogenesis (by 11-35%), infarction area was reduced by 30% and the left ventricular wall was 46% thicker (P<0.05). The results indicated that hAng1-modified MSCs improved heart function, followed by angiogenic effects in salvaging ischemic myocardium and reduced cardiac remodeling.
Sun
Lijie
L
Department of Cardiology, Peking University Third Hosptial, Beijing 100083, China.
Cui
Ming
M
Wang
Zuoyan
Z
Feng
Xinheng
X
Mao
Jieming
J
Chen
Ping
P
Kangtao
Ma
M
Chen
Fengrong
F
Zhou
Chunyan
C
D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000254:growth & development; D015153:Blotting, Western; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods*; D014162:Transfection
D042683:Angiopoietin-1; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins