Investigate The Effect Of Bone Marrow Mesenchymal Stem Cells Transplantation On The Expression Of Matrix Metalloproteinase-9 And Tissue Inhibitors Of Metalloproteinase-1 In Heart Failure Of Wister Rats

BackgroundHeart failure is one of the most important cardiovascular diseases, with high mortality, and invasive treatment such as mechanical circulatory support and cardiac transplantation is sometimes required for severe heart failure. Cell therapy is an attractive therapeutic strategies are used in clinical practice for cardiovascular diseases,But resecent studies have suggested benefits of stem cells transplantation for the regeneration of cardiac tissue and function improvement of regionally infracted myocardium.As a cell source, various kinds of stem cells such as bone marrow cells, endothelial progenitor cells, mesenchymal stem cells (MSC) and cardiac stem cells have been in transplantation. Especially, bone marrow-derived MSC possess multipotency and can be easily expanded in culture.Cardiomyocyte dropout (necrosis and apoptosis)and interstitial remodeling play a critical role in the progress of CHF.MSCs can not only migrate into the damaged heart anddifferentiate into specific cell types such as cardiomyocytes and improve the heart function but also induce the expression of Matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 on interstitial remodeling. ObjectiveTo investigate the effect of bone marrow mesenchymal stem cells transplantation on heart function and expression of Matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in doxorubicin induced heart failure of Wister rats .MethodsTo establish a rat model of heart failure, Adr was given intraperitoneally to Wister rats (n=30) weekly at a dose of 2.5mg/kg body weight for 6 weeks.The surviving animal models (n=21) were then randomly divided into the cell transplantation group (n=11) and the transplantation control group (n=10).select normal control group (n=8) injected saline. MSCs were isolated,purified and amplified with Dulbecco's modified Eagle's medium (DMEM) containing 12 % fetal bovine serum (FBS) in ex vivo. Cells at the third passage were identified with a flow cytometer and were marked with 5-Bromo-2'-Dexuuridine (BrdU) before transplantation. One week after the last administration of Adr, BrdU-labeled MSCs (5×106 cells) were transplanted into heart failure models of cell transplantation group through tail vein. The transplantation control group was injected by equivalent volume culture medium (DAEM). Normal control group were injected by saline. Four weeks after the transplantation, the heart function and ventricular remodeling were evaluated by echocardiography. Pathological changes were measured and immunochemical analysis was performed .ResultsFlow cytometric analysis showed that the MSCs of third passage cultured in vitro expressed CD44 surface marker (99.7%±0.9%). Four weeks after transplantation, BrdU-labeled transplanted MSCs could be found in the hearts of the recipients. Immunochemical staining revealed that Matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP-1) were significantly difference in transplantation group in contrast with The transplantation control group and normal control group(p<0.05).Immunochemical staining revealed that the engrafted stem cells expressed CX-43.The amount of collagen reduces in MSCs transplantation group. The LVEF of MSCs transplantation group and DMEM transplantation group and normal control group were (87.26±1.64) % , (72.42±2.46) % , and (93.60+1.54)%, respectively ( P < 0. 05) . MSCs significantly improved the heart function ( P < 0. 05)as compared with transplantation control group .ConclusionIntravenously transplanted MSCs can not only migrate into the damaged heart and improve the heart function but also induce the expression of Matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 on interstitial remodeling of rat with doxorubicin induced rats heart failure.