| Objective:To dual-monitor the survival, proliferation and migration of SD rat bone marrow mesenchymal stem cells expressing green fluorescent protein and firefly luciferase (GFP/Fluc BMSCs) transplanted into acute infarcted myocardium of Balb/c mice and to evaluate the improvement of cardiac function by bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Further more, to promote the localization and survival of GFP/Fluc BMSCs in myocardium and enhance the therapeutic effect by co-injection with functionalized self-assembling peptide nanofiber scaffold RADA-PRG orRADA-KLT.Method:Acute myocardial infarction of Balb/c mice was induced by ligation of anterior descending coronary artery. Group A (control group) was treated with PBS, Group B with GFP/Fluc BMSCs, Group C with GFP/Fluc BMSCs+RADA-PRG, and Group D with GFP/Fluc BMSCs+RADA-KLT. The injection volume was 40ul per mouse, and the concentration of GFP/Fluc BMSCs was 1.0×106/ml. BLI was performed at day 1,4,7, 10 and 13 after transplantation. MRI was performed and left ventricular ejection fraction (LVEF) was calculated at day 3 and 28. HE staining and immunohistochemical analysis of GFP and CD34 was performed at day 29.Results:BLI signals were detected on the heart region of Group B, C and D at day 1, and peaked at day 4, but decreased since day 7 gradually. The signals of Group B and D disappeared at day 10, and that of Group C disappeared at day 13. No signal was detected from Group A all along. The signal intensity of Group C was significantly higher than Group B since day 4 (day 4, P=0.0008; day 7, P=0.003; day 10, P=10-7), while that of Group D was higher than Group B only at day 4 (P=0.02). For Group B, C and D, BLI signals were detected out of the heart region since day 1, especially on head region, and disappeared at the same time as those on heart region. At day 3, there was no significant difference of LVEFs between four groups (P=0.59). At day 28, LVEFs of four groups all improved. There was still no significant difference between LVEFs of Group A and B (P= 0.21), but LVEFs of Group C and D were both higher than those of Group A (Group C, P=0.01; Group D, P=0.01) and B (Group C, P= 0.01; Group D, P=0.02). HE staining showed fibrous scar tissue within infarcted foci. Immunohistochemical analysis of GFP found GFP positive cardiomyocytes from Group B, and GFP positive cells from Group C and D, while failed from Group A. Immunohistochemical analysis of CD34 showed positive cells within infarcted foci of four groups, and the densities of vascular structure of Group B, C, D were higher than Group A (Group B, P=0.006; Group C, P= 0.0001; Group D, P=0.0002), and those of Group C and D were higher than Group B (Group C, P=0.003; Group D, P=0.002).Conclusion:Dual-monitored by BLI and MRI, the survival, proliferation and migration of SD rat GFP/Fluc BMSCs transplanted into acute infarcted myocardium of Balb/c mice could be followed, and the improvement of cardiac function could be evaluated. Further more, the localization and survival of GFP/Fluc BMSCs in myocardium was promoted by co-injection with RADA-PRG, and the therapeutic effect was both enhanced by co-injection with both RADA-PRG or RADA-KLT.
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