Bone Marrow Mesenchymal Stem Cells For Myocardial Infarction Repair Mechanisms

Object: MSCs isolated from bone marrow of adult animals or patients are both molecularly and functionally heterogeneous and are capable of differentiating into adipocytes, chondrocytes, myoblasts, osteoblasts, and hematopoiesis-supporting stroma. In this experiment, MSCs were isolated, cultured and checked the potency of differentiating into cardiomyocytes. At the same time, try to decide the more suitable phase and amount of treatment of myocardial infarction by MSCs transplantation. Methods: Mesenchymal stem cells were recovered from a ficoll gradient and treated with 5-azacytidine in vitro. After two weeks, some samples carried out hematoxylin-eosin staining and other samples performed immunofluorescence staining. In vivo, a ligation model of left coronary artery of rats was used. Three days after myocardial infarction and four weeks after myocardial infarction, mesenchymal stem cells labeled with 4,6-diamidino-2-phenylindole were injected into the abnormal heart of therapy groups. According to the different amount of transplanted MSCs, the therapy group divides to the group of large dose (107/kg body weight) and small dose (107/kg body weight), too. Meanwhile culture medium was injected in the abnormal heart of control groups. Four weeks after transplantation, rats of control group and therapy group underwent transthoracic echocardiography and immunofluorescence studies. Results: In vitro, after two weeks, these cells presented some features of cardiomyocytes and immunofluorescence analysis revealed these cells expressed connexin 43. In vivo, four weeks after implantation, echocardiography showed an improvement on left ventricular performance in the large dose therapy-acute myocardial infarction group compared with the corresponding control group and the left ventricular performance in the small dose group and the corresponding control group has not significant differentiation. The left ventricular performance in the old myocardial infarction groups hardly improved. Histology results showed that mesenchymal stem cells transplanted into abnormal hearts, and then differentiated to myocardium and expressed connexin 43 in the large dose therapy -acute myocardial infarction group. But in other therapy groups, hardly engrafted cells were observed. Conclusions: In vitro, the results showed that MSCs had the potency of differentiating into cardiomyocytes. In vivo, administration of syngenic MSCs into the heart of myocardial infarcted rat was safety demonstrated and the results showed that MSCs engraftment should be executed at the early phase of myocardial infarction. In addition, the amount of MSCs will affect the result of transplantation and it must exceed 105/kg body weight.