Objectives To trace and evaluate intracoronary transplanted mesenchymal stem cells(MSCs) labeled with superparamagnetic iron oxide(SPIO) by using magnetic resonance imaging(MRI) in a swine model of myocardial infarcti...Objectives To trace and evaluate intracoronary transplanted mesenchymal stem cells(MSCs) labeled with superparamagnetic iron oxide(SPIO) by using magnetic resonance imaging(MRI) in a swine model of myocardial infarction (MI).Methods MSCs were transfected with a lentiviral vector carrying the gene encoding green fluorescent protein (GFP) and labeled in vitro with SPIO.Two weeks after MI, swine were randomized to intracoronary transplantation of dual -labeled MSCs(n = 10),MSCs-GFP(n = 10) and saline(n = 5).MRI examination was performed with a 1.5T clinical scanner at 24 hours,3 weeks and 8 weeks after cells transplantation. Signal intensity(SI) changes,cardiac function and MI size were measured using MRI.Correlation between MR findings and histomorphologic findings was also investigated. Results The labeling efficiency at a combination of 25μg Fe/ml SPIO and 0.8 pi/ml Lipofectamine 2000 reached 100%.SPIO labeling did not affect GFP fluorescence and dual-labeling did not affect cell proliferation(P】0.05). Multipotentiality was not affected especially for cardiomyocyte-like cells differentiation.Cardiac cell marker of a-MHC and actinin were positively expressed by immunofluorescence staining after induction.SI on T2 * WI decreased substantial- ly in the interventricular septum 24 hours after injection of MSCs.The intensity of hypo-intense signals appeared to increase throughout the later time points.Changes in SI at 24 hours,3 weeks and 8 weeks were 52.98%±10.74%,21.53%±5.40%and 6.23%±2.01%,respectively(P【0.01).DE-MRI demonstrated both dual-labeled MSCSs and MSCs-GFP could dramatically reduce the size of MI and improve cardiac function. Histological data revealed that prussian blue stain-positive cells were found mainly in the border zone which also showed green fluorescence but negative for macrophage marker(CD68).Gross pathologic examination revealed that engrafted MSCs dramatically reduce the extent of necrotic myocardium and promote the regeneration of new,contractile myocardium along the subendocardial surface of the MI. Conclusions MSCs could be efficiently and safely labeled with SPIO and GFP,and could be detected reproducibly and noninvasively in vivo using cardiac MRI.Intracoronary transplantation of dual-labeled MSCs could increase cardiac function and reduce the size of MI.展开更多
文摘Objectives To trace and evaluate intracoronary transplanted mesenchymal stem cells(MSCs) labeled with superparamagnetic iron oxide(SPIO) by using magnetic resonance imaging(MRI) in a swine model of myocardial infarction (MI).Methods MSCs were transfected with a lentiviral vector carrying the gene encoding green fluorescent protein (GFP) and labeled in vitro with SPIO.Two weeks after MI, swine were randomized to intracoronary transplantation of dual -labeled MSCs(n = 10),MSCs-GFP(n = 10) and saline(n = 5).MRI examination was performed with a 1.5T clinical scanner at 24 hours,3 weeks and 8 weeks after cells transplantation. Signal intensity(SI) changes,cardiac function and MI size were measured using MRI.Correlation between MR findings and histomorphologic findings was also investigated. Results The labeling efficiency at a combination of 25μg Fe/ml SPIO and 0.8 pi/ml Lipofectamine 2000 reached 100%.SPIO labeling did not affect GFP fluorescence and dual-labeling did not affect cell proliferation(P】0.05). Multipotentiality was not affected especially for cardiomyocyte-like cells differentiation.Cardiac cell marker of a-MHC and actinin were positively expressed by immunofluorescence staining after induction.SI on T2 * WI decreased substantial- ly in the interventricular septum 24 hours after injection of MSCs.The intensity of hypo-intense signals appeared to increase throughout the later time points.Changes in SI at 24 hours,3 weeks and 8 weeks were 52.98%±10.74%,21.53%±5.40%and 6.23%±2.01%,respectively(P【0.01).DE-MRI demonstrated both dual-labeled MSCSs and MSCs-GFP could dramatically reduce the size of MI and improve cardiac function. Histological data revealed that prussian blue stain-positive cells were found mainly in the border zone which also showed green fluorescence but negative for macrophage marker(CD68).Gross pathologic examination revealed that engrafted MSCs dramatically reduce the extent of necrotic myocardium and promote the regeneration of new,contractile myocardium along the subendocardial surface of the MI. Conclusions MSCs could be efficiently and safely labeled with SPIO and GFP,and could be detected reproducibly and noninvasively in vivo using cardiac MRI.Intracoronary transplantation of dual-labeled MSCs could increase cardiac function and reduce the size of MI.
