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Studies On Migration And Its Mechanism In Bone Marrow Mesenchymal Stem Cell Transplantation For Myocardial Infarction In Rats

Posted on:2005-06-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:L MengFull Text:PDF
GTID:1104360122992031Subject:Department of Cardiology
Abstract/Summary:PDF Full Text Request
Bone marrow-derived stem cells including mesenchymal stem cells (MSCs), Lin"ckit+ bone marrow stem cells, ect, could regenerate myocardium, participate in vasculogenesis and improve ventricular function. Thus bone marrow stem cell therapy is a promising approach for myocardial infaction (MI) and congestive heart failure after MI.Firstly, bone marrow-derived MSCs were delivered intravenously to repair injured myocardium in this study. Its feasibility and safety were tested in rat model after MI. The migration, differation and tissue distributions of infused MSCs were observed in rat. In particular, it was investigated whether infused MSCs migrated to target organ of myocardium. 20 male Wistar rats were selected at random into three groups: acute myocardial infarction (AMI) group (n=8), normal control group (n=6), sham MI group (n=6). Animal models were established by ligating the left anterior descending branch of coronary artery. Then 24h later, the DAPI (4',6-diamidino-2-phenylindole) labeled exogenous MSCs were infused intravenously in rats. Four weeks after the infusion, the rats were killed and their hearts and other organs were harvested for histological examination. It was observed that DAPI labeled MSCs with blue nuclei were only in the infracted myocardium and theirperipheral regions, but not in the normal myocardium remote from MI in AMI rats and not in the normal myocardium in rats of the other two groups. Infused MSCs distributed mainly in the lung, liver and spleen of all rats. No lymphocyte proliferation appeared in the myocardial tissues of all rats. It occurred with no tumorigenesis. Therefore it was concluded that MSCs delivered by intravenous infusion could migrate to the infarcted myocardium and express the phenotype of myocardium, but not migrate to the normal one. Intravenous delivery of MSCs to the infarcted myocardium is feasible and safe.Secondly, in vivo the tissue distributions of infused MSCs intravenously labeled with 99mTc-HMPAO were tested in series by emission computer tomography (ECT). The migration within infracted myocardium and tissue distributions of infused MSCs were also evaluated quantificationally by well counter. In this study, it showed that MSCs could be labeled with 99mTc-d,l-HMPAO and that the cell viability of MSCs is 95% after labeled while its adhesion character and proliferation ability aren't altered. 3 hours after infusion, the radioactivity accumulation appeared hi lung, and it revealed that the infused cells distributed mainly in lung, and some appeared in liver, spleen, kidney and bladder. 6 hours after infusion, the radioactivity in lung diminished compared with that at 3 hours after infusion, andbilateral kidneys imagine appeared intensively. 9 hours after infusion, the radioactivity in lung appeared reduced significantly than that at 3 hours after infusion, and liver imagined increasedly, intestine tract imagine appeared in several rats. This study indicated that the track of infused MSCs intravenously reveals that they are captured earlier mainly in lung, and then redistributes to other organs. It also suggested that in vivo to tracing the 99mTc-HMPAO labeled MSCs is feasible. The results of well counter showed that the ratio of T/N of whole heart in MI rat isn't different from that in normal one. However, within rat heart, the radioactivity of infarcted myocardium increases significantly than that of non-infarcted one, and the radioactivity of myocardium in non-infarcted zone is lower than that in whole heart. This suggested that infarcted myocardium may induces the migration of infused MSCs to redistribute in vivo for repair of the injured tissue. Our data indicate that transplantation with MSCs intravenously for repair of myocardium is potential, but there still exists some difficulties in application. It is necessary to further investigate mechanisms in chemotaxis and cell migration in order to enhance the transplanted cells migration into target tissue.Thirdly, the chemotaxis effect of ischemic myocardial tissue on MSCs was investigated in vitr...
Keywords/Search Tags:bone marrow mesenchymal stem cell, cell transplantation, myocardial infarction, migrate, 99mTc-HMPAO, tissue distribution, monocyte chemotactic protein-1
PDF Full Text Request
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