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Human Bone Marrow-derieved Mesenchymal Stem Cells Transplantated Into The Damaged Heart To Improve Heart Function

Posted on:2004-05-04Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q FanFull Text:PDF
GTID:2144360092990773Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background.Congestive heart failure is the end stage of all kinds of cardiovascular diseases. Myocardial infarction (MI) is life-threatening event that may cause sudden cardiac death and heart failure. Despite considerable advances in diagnosis and treatment of heart disease, cardiac dysfunction after MI is still the major worldwide cardiovascular disorder. Post acute MI, the damaged myocardium is gradually replaced by fibrotic noncontractile cells to form scar tissue. The ventricular remodels. The developing ventricular dysfunction is primarily due to a massive loss of cardiomyocytes. Although heart transplantationis an option for patients in severe congestive heart failure, organ shortage and the need for immunosuppression detract from whole organ transplantation. In 1990s some study showed that transplanted fetal smooth muscles , skeletal myoblast cells and cardiomyocytes should limited scar expansion and prevent onset or development of heart failure, but these cells were eventually eliminated by rejection. Recently some research showed after transplantated into the myocardial infarction region, the bone marrow-derived mesenchymal cells could transdifferente into cardiomyotes and improve heart function. This study tested the feasibility of human bone marrow-derived mesenchymal cells could differentiate into cardiomyotes in the MI region of Neawland rabbits and autologous bone marrow-derived mesenchymal cells transplantation could improve heart function of primary dilatedcardiomyopathy patients.Methods.Bone marrow were obtained from health men by biopsy, heparin was used to anti-thrombosis. Human MSCs and red cells were seperated by the gradient centrifugation method. 1.073g/ml gradient percoll was used. DMED with 10%fetal bovine serum, penicillin G [100U/ml] and streptomvein [100U/ml] was used to culture hMSCs and their number expanded. FCM was used to analysis the superf icial markers of CD34, CD45, CD166 and CD29 of hMSCs. The proliferation and growth characteristics were observed in primary and passage culture.New Zealand rabbits were randomly divided into myocardial infarction(MI) group and human bone marrow-rerived mesenchymal stem cells transplantation (MI+MSCs) group. Myocardial infarction was induced by ligation of left coronary artery. The hMSCs were marked by BRDU before 48h of the transplantation. The rabbits of MI+MSCs group, were treated with 5 ×106 hMSCs transplantated into myocardial infarction region after 1h of ligation of coronary artery; Cyclosporin A Oral Solution 10mg/kg was given before 24h of the surgery and post surgery once a day for 4weeks. The MI group were received PBS. Ecocardiography was given in each group before surgery and after 4 weeks. The hearts were harvested for HE, anti-BRDU and anti-troponin I imrnunohistochemistry pathological examination.In the primary dilated cardiomyopathy patients, 20ml bone marrow was obtained by biopsy and hMSCs were separated by the gradient centrifugation method. 1.073g/ml gradient percoll was used. 1× 107 autologous hMSCs were transplantated into the cardiac tissue through coronary artery by JR4.0 cather. Before and after the hMSCs transplantation for 1month, cardiac ECT, echocardiogram and holter was performed. Results.1. Human bone marrow-derived MSC showed active proliferative capacity in vitro primary and passage culture. Cell markers CD29 and CD 166 are positive, but CD34 and CD45 are negative2. EF of MI+MSCs group (0.695±0.038) were higher than MI group (0.554 ± 0.065 ) after 4 weeks(P<0.05). BRDU marked hMSCs were survived in the myocardial infarction region and transdifferentiated into cardiomyocytes, improved heart function.3. After autologous hMSCs transplantation in the primary dilated cardiomyopathy patients, cardiavascular infusion improved, EF enhanced from 30.9% to 41% and heart function improved. Holier showed no Premature beats and ventricular tachycardia occurd.Conclusions.1. Human bone marrow-derived MSC showed active proliferative capacity in vitro prim...
Keywords/Search Tags:Human bone marrow-derived mesenchymal stem cells, Transplantation, Acute Myocardial Infarction, Heart failure.
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