| Objective:This study was designed to analyze the main organ(heart, liver, spleen, kidney) re-distribution of stem cells by ICI in a swine myocardial infarction (MI) model using magnetic resonance imaging(MRI).Materials and Methods:Bone marrow-derived esenchymal stem cells were obtained from male swine and labeled with iron oxide during culture. One week after creation of a myocardial infarction in female swine, the survivors were randomly divided into 2 groups, group stem cells transplantation and control. In group stem cells transplantation spio labeled stem cells (1×108) were infused through coronary and the saline was infused by the same way. Three days later, cell distribution was assessed by T2* change with magnetic resonance imaging and sex-determining region on Y-chromosome (SRY) with quantitative polymerase chain reaction.Results:The changes of T2* value in stem cell transplantation before and after transplantation of heart, liver, spleen and kidney were -9.03±1.06,-4.58±0.38,-13.2±0.93 and -4.33±1.08, while those value in control group were -0.22±1.11 (P<0.001), 1.63±1.62 (P=0.004),0.65±1.51 (P<0.001) and -1.40±1.56 (P=0.154). SRY gene RT-PCR were positive for stem cell group, while results of the control group was negative. Prussian blue staining showed positve cells in the transplanted groups, which was in good agreement with the MRI findings.Conclusion:Using SPIO labeled stem cells, MRI can be used as a convenient and effective means of tracing the migration of stem cells in vivo in the early stage after transplantation. The majority of BMSCs transplanted by ICI would be entrapped by the extracardial organs. the spleen is a major re-distribution of organs. Objective:To investigate the effects of autologous bone marrow-derived mesenchymal stem cells (MSCs) transplantation on acute myocardial infarction in swine models by Magnetic Resonance Imaging (MRI).Materials and Methods:Fourteen Chinese mini-pigs (27±3Kg) were divided into 2 groups, including group control (n=7) and group 2 (group transplantation, n=7). Myocardial infarction models were made by occlusion of left anterior descending coronary artery for 90 minutes. Then autologous MSCs (3x106 cell/ml) with a volume of 10 ml were injected into LAD by over-wire-balloon catheter at one week after AMI. The potentials of differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were detected at baseline (1 week after AMI) and endpoint (6 weeks after transplantation) magnetic resonance imaging (MRI).Results:MRI showed that all parameters at baseline were not significantly different between 2 groups. At endpoint, there were severe fibrosis and inflammatory cell infiltration observed in infarcted region with seldom surviving myocardium in group control, in contrast, there were less fibrosis and inflammatory cell infiltration in group 2 with more surviving myocardium. In group 2, left ventricular ejection fraction (LVEF) increased from 42.8±7.8%to 49.1±9.5%, which was significantly different from that in group control (.P<0.001). In addition, the number of dyskinetic segments in infarcted region (P<0.0001), scar volume (P<0.0001) and ratio of scar tissue to left ventricule mass (P<0.05) were decreased in group 2 compared with group control. However, end-systolic and end-diastolic volume didn't decreased significantly compared with that in group control (P>0.05). Immunofluorescent staining showed that DAPI-labeled cells in infarcted and peri-infarct region were positive for cardiomyocyte-specific troponin T and connexin 43, and vessel-specific smooth muscle actin, which indicate that implanted MSCs survived, differentiated into and connected to cardiomyocytes in vivo. Capillary density in both infarcted-and peri-infarct region of group 2 was much more than that in group control (P<0.001).Conclusion:Our study demonstrated the following:(1) catheter-based delivery of autologous bone marrow-derived MSCs into infarcted myocardium is feasible and effective; (2) MRI is a reliable means to assess the effects of stem cell transplantation in infarted models of swine. Part 3Effects of Autologous Bone Marrow Mononuclear Cells Transplantation through Coronary Artery Bypass Grafting in Patients with Chronic Myocardial Infarction Assessed by Magnetic Resonance Imaging:A Randomized, Double Blind, Placebo-controlled Pilot TrialObjective:Recent studies have shown that autologous bone marrow mononuclear cell (aBM-MNC) transplantation can be effectively performed in human beings either by the coronary route or by endoventricular injections. However, scanty data are available for patients undergoing coronary artery bypass grafting (CABG). Accordingly, the aim of this study was to use an "one-stop" non-invasive imaging examination-MRI to evaluate the feasibility and safety of aBM-MNC transplantation in patients with chronic myocardial infarction(MI) undergoing CABG.Materials and Methods:We did a randomised, double-blind, placebo-controlled study in 50 patients (male=47, female=3, age 57.48±7.98y) with Chronic MI. The patients were randomly divided into 2 groups(group A:CABG+aBM-MNC, group B: CABG only). Preoperative global left ventricular functions and scar tissue were measured by MRI. The therapeutic effects were assessed by MRI one year after aBM-MNC transplantation.Results:All the patients were treated without major complications. There is no evidence of new ventricular arrhythmia or neoplasia. The LVEF was improved 13.5%in group A, while 8.04%in group B(P=0.04), LVEDV/m2 and LVESV/m2 were decreased by 24.21±5.86ml/m2 and 29.22±5.05 ml/m2, respectively, which were significantly different from that in group B [3.13±7.23 ml(P=0.028) and 7.71±5.93(P=0.008)]. The cardiac output(CO),cardiac index(CI) and cardiac mass(CM) didn't show significant difference between the two groups. Compared with group B, aBM-MNC group was associated with no statistical significant reduction in myocardial infarct size (9.4%vs. 6.0%, P=0.100).Conclusion:Comprehensive in vivo CMR reveals reversed remodeling and improved systolic function and scar characteristics after aBM-MNC transplantation. CABG+aBM-MNC transplantation can lead to comparable improvements of left ventricle in chronic myocardial infaction. |
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