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The Effects Of Intracoronary Transplantation Of Different Types Stem Cells On Heart Function In Chronic Heart Failure And It's Mechanism

Posted on:2006-12-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z C FanFull Text:PDF
GTID:1104360155473664Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
[Background] Stem cell transplantation is a promising strategy for treating myocardial infarction or/and chronic heart failure(CHF). The feasibility of introcoronary stem cells implantation into dilated cardiomyopathy hearts is unclear.Meanwhile, the certain mechanisms of stem cells transplantation to treat chronic heart failure(CHF) is also unclear. [Objective] In this study, we assessed the feasibility of introcoronary stem cells implantation into dilated cardiomyopathy hearts using a rabbit model.Meanwhile,we also investigated the changes of heart function , left ventricular endostolic diameter(LVED) , cardiomyocyte membrane Na+/K+ ATPase(CMNKA) and sarcoplasmic reticulum membrane Ca2+ATPase (SERCA) activity after different types stem cells transplantation in CHF,whether different kinds stem cells transplantation would affect heart function and ATPases activity to a similar degree. [Methods and Results] Japanese white ears rabbits were used as CHF models by intravenously injecting adriamycin. Autologous bone marrow mononuclear cells(BMCs), bone marrow stromal cells (MSCs), skeletal myoblasts (SMs) or culture medium were introduced into coronary arteies by occluding the root of ascending aorta. The mortality in the operation was 7. 1%%, the mortality was 16. 7% in 4 weeks. After 4 weeks,heart function was evaluated by two-dimensional ecocardiography. In BMCs group(n=8), the ejection fraction (EF) had significant improvement(from72.13±7.06% to 81.54 ± 5.52%,p<0.05). No significant difference was seen in MSCs(n=8) , SMs(n=6) and sham groups(n=8) compared with pretransplantation (77.63 ± 4.41%vs 80.75 ± 6.50%; 76.50 ±8.94% vs 75.67±14.33%;72.38 + 5.95%vs70.46+11.45%;p>0.05).In sham group,the LVED hadsignificant enlargement (from 1.31+ 0.25mm to 1.51+ 0.20mm, p<0.05), No significant difference was seen in MBCs> MSCs and SMs groups compared with pretransplantation( 1.22+1.25mm vs 1.25 + 0.17mm; 1.24 +0.07mm vs 1.33 + 0.13mm; 1.31+0.24 mm vs 1.41+0.28mm;p>0.05). The CMNKA activity in all cell types stem cell transplantation groups had significant improvement (p<0.05).The CMNKA activity in SMs increased significantly compared with the control group n BMCs and MSCs groups. The SERCA activity had tendency of improvement,but no significance were seen in all types stem cells transplantation groups compared with sham group(p > 0.05). Immunofluorescence revealed de novo expression of cardiac troponin I in BMCs and MSCs groups,in SMs group, cardiac troponin I was not detected. [Conclusions] Intracoronary cell transplantation could provide effective cell delivery into dilated cardiomyopathy hearts and could be a useful strategy for treating CHF.BMCs and MSCs engafted in the myocardium appeared to differentiate into cardiomycytes.BMCs transplantation may be thefirst selection in all above types cells. Intracoronary cell transplantation could improve the CMNKA activity and had tendency of improvement the SERCA activity in CHF.It may be one of mechanisms of stem cell transplantation to treat CHF.
Keywords/Search Tags:heart failure, cell transplantation, heart function bone, Na~+/K~+ATPase, Ca2+ATPase
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