Immuno-inflammatory regulation effect of mesenchymal stem cell transplantation in a rat model of myocardial infarction.
BACKGROUND
Mesenchymal stem cells (MSC) have recently been shown to possess immunomodulatory properties in vitro and in vivo. The present study aimed to investigate the regulatory effect of MSC transplantation on the immuno-inflammatory response in myocardial infarction (MI).


METHODS
MI was induced in Sprague-Dawley rats by left anterior descending coronary artery ligation, and the animals were randomly assigned into the following three groups: sham ( n=8); phosphate-buffered saline (PBS) injected (MI+PBS, n=8); and MSC transplantation (MI+MSC, n=8). BrdU-labeled MSC or PBS was transplanted into peri-infarct myocardium by direct myocardial injection. At 1 and 28 days post-transplantation, cardiac function was evaluated by echocardiography. Transplanted cells were investigated through immunohistochemistry. Lymphocyte cytotoxic activity was evaluated with the crystal violet method. The activity of NF-kappaB and protein expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-10 in myocardium were assessed by immunohistochemistry and Western blot.


RESULTS
Echocardiographic examination revealed that the MSC transplantation prevented left ventricular dilation and dysfunction at 28 days after the operation. BrdU-stained cells were found living in host heart 4 weeks after transplantation. MSC transplantation attenuated the cytotoxic activity of spleen lymphocytes. Transplantation of MSC inhibited the activity of NF-kappaB, attenuated the protein production of TNF-alpha and IL-6, and increased the expression of IL-10 in peri-infarct myocardium.


CONCLUSIONS
MSC transplantation modulated the immuno-inflammatory response in MI. The immuno-inflammatory regulatory effect of MSC transplantation might partly account for the cardiac protection in myocardial infarction.
Du
Y-Y
YY
Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Zhou
S-H
SH
Zhou
T
T
Su
H
H
Pan
H-W
HW
Du
W-H
WH
Liu
B
B
Liu
Q-M
QM
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000517:prevention & control; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004452:Echocardiography; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000276:immunology / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D016753:Interleukin-10; D015850:Interleukin-6; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase