Effect of transplanted mesenchymal stem cells from rats of different ages on the improvement of heart function after acute myocardial infarction.
BACKGROUND
Mesenchymal stem cells (MSCs) transplantation is of therapeutic potential after ischemic injury in both experimental and clinical studies. Clinically, elderly patients are more vulnerable to acute myocardial infarction (AMI). But little is known about the characteristics of young donor-derived MSCs transplanted to old patients with AMI. The present study was designed to investigate the effect of transplanted MSCs from rats of different ages on the improvement of heart function after AMI.


METHODS
MSCs from Sprague-Dawley (SD) rats were isolated and cultured in vitro. The apoptosis characteristics of MSCs were observed under conditions of ischemia and anoxia. SD rats underwent MI received intramyocardial injection of MSCs from young donor rats (n = 8), old donor rats (n = 8), respectively. AMI control group received equal volume physiological saline. Immunofluorescence was used to observe the differentiation of the grafted cells into cardiomyocytes. Four weeks after cell transplantation, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry for vascular endothelial growth factor (VEGF), VIII-factor immunohistochemistry for vessel density, TUNEL, caspase-3 for cardiomyocyte apoptosis, echocardiography and hemodynamic detection for heart function were performed.


RESULTS
The apoptosis rate of the old donor-derived MSCs group was significantly higher than that of the young donor-derived MSCs group under conditions of ischemia and anoxia (P < 0.05). Engrafted MSCs survived, proliferated and differentiated into myocardium-like cells. VEGF gene expression and capillary density in the old donor-derived group were lower than those in the young donor-derived group but higher than those in the control group (P < 0.05). The transplantation of old donor-derived MSCs attenuated apoptosis of cardiomyocytes in the peri-infarct region compared with the control group and the effect was elevated in young donor-derived MSCs (P < 0.05). The heart functions (left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS)) were improved more significantly in the old donor-derived MSCs group than in the control group and the heart function in the young donor-derived MSCs group further improved (P < 0.05).


CONCLUSIONS
Young donor-derived MSCs can improve heart function significantly through angiogenesis and decreasing cardiomyocyte apoptosis when transplanted to the infarcted area.
Wang
Yi-qing
YQ
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, China.
Wang
Miao
M
Zhang
Peng
P
Song
Jing-jin
JJ
Li
Yuan-peng
YP
Hou
Shu-hong
SH
Huang
Cong-xin
CX
D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D053148:Caspase 3