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Differentation Of Bone Marrow Stromal Cells To Myocardio-cytes And Its Application In Myocardioplasty

Posted on:2004-12-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Z LuFull Text:PDF
GTID:1104360092995548Subject:Department of Cardiology
Abstract/Summary:PDF Full Text Request
Dispite the recent remarkable progress in medical and surgical treatment for heart failure, end-stage heart of failure, mostly, of ischemic origin, has still a major cause of death worldwide. Adult cardiomyocytes lacks the ability to regenerate after ischemic injury, death of cardiomyocytes and the replacement of muscle by scar tissue leads to loss of contractile function, and consequently, promotes a progressive heart failure. Thus, the present therapies can't recovery the contractile cardiomyocytes. Cardiac transplantation and mechanical support using left ventricular assist system implantation have been well accepted as the ultimate lifesaving means of supporting these patients. However, these treatments have limitations such as donor shortages, rejection, infection for cardiac transplantation, and so on. In these circumstances, alternative treatments with new concept have developed. The recent development of cellular cardiomyoplasty has offered a new approach to restore impaired heart function.The fetal cardiomyocytes have been the first to be investigated and the only ones to show a real strctural and functional integration into the recipient myocardium, but it is much more immunogenic so that clinical transpantation would requirelifelong immunosuppression. The challenge of using embryonic cells is still greater. Sensitive ethical and regulatory issues are currently generation a state of turmoil in many western countries.The cardiomyocytes autograft is limited for its origin. Fibroblasts autograft may improve postinfarction diastolic performance but are unable to augment contract contractile function. Likewise, smooth muscle cells limit dilatation of the left ventricle but are unlikely to significantly impact on systolic performance. Satellite cells differentiate into mature skeletal muscle and do not express cardiac-specific genes after grafting into the heart.Bone marrow stromal cells (BMSCs) are pluripotent cells to be differentiated into cardiomyocytes, which can be used for cellular cardiomyoplasty. It offers serveral advantages on cell transplantation for the treatment of heart failure: (1) a commitment to a well-differentiated myogenic lineage and vascular structure; (2) no immunic factors; (3) an autologous origin which is a key factor for large-scale clinical applicability; (4) the developent of straightforward procedures allowing growth of a large number of cells from a small biopsy; which makes the risk of tumoreginic lineage which makes the risk of tumoregincity extremely low; (5) a high resistence to ischemia, which is a major advantage given the hostile environment in which they are intended to be implanted. Generally, Bone marrow stromal cells are idea seed cells for cellular cardiomyoplasty.In this study, we explored bone marrow stromal cells on itsbiogical properties, differentiation to cardiomyocytes and autograft to treat acute myocardial infarction.This thesis consists of three partsParti Culture and proliferation of bone marrow stromal cells in vitroTo establish a method of isolating, culturing rat bone marrow stromal cells (BMSCs) in vitro, and explore their biogical properties and growth effects of ginsenoside Rgt on them. The results showed that bone marrow stromal cells show table growth, easy survival and rapid proliferation in present adherant culture condition and exhibit infantility in its ultrastructures and cell cycle. The subcultured bone marrow stromal cells poss multipotential differentiation. Ginsenoside Rg, could promote proliferation of swine bone marrow stromal cells in vitro. Part2 Study of Cardiomyocytes generated from bone stromal cells in vitroTo observe the morphological changes, beta-myosin heavy chain and atrial natric peptide expression, beta adrenoceptors density, calcium waves of 5-azacytidine-induced bone marrow stromal cells in vitro. Results showed that normal cultured bone marrow stromal cells do not express beta-myosin heavy chain, atrial natric peptide or beta adrenoceptors. After treated with 5-azacytidine...
Keywords/Search Tags:Bone marrow stromal cell, 5-azacytidine, acute myocardial infarction, differentation, cellular cardiomyoplasty
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