Background Mesenchymal stem cells （MSCs） transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent ...Background Mesenchymal stem cells （MSCs） transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs （MR-MSCs） and monitor the restorative effects of MR-MSCs with magnetic resonance （MR） imaging. Methods Acute myocardial infarction （AMI） was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat （SPSS version 12.01）. Results A total of 26 swine were divided into four groups （sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7）. MSCs, MR-MSCs （10~cells） or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction （LVEF） was slightly increased in the AMI group （（41.87~2.45）% vs （39.04~2.80）%, P 〉0.05）, but significantly improved in the MR-MSCs group （（56.85~1.29）% vs （40.67~2.00）%, P 〈0.05） and unlabeled group （（55.38~1.07）% vs （41.78~2.08）%, P 〈0.05） at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Conclusion Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2- month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.展开更多
Background Superparamagnetic iron oxide （SPIO） particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging （MRI）. Micrometer-sized superparamagnetic iron oxi...Background Superparamagnetic iron oxide （SPIO） particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging （MRI）. Micrometer-sized superparamagnetic iron oxide （MPIO）particles and nanometer-sized ultrasmall superparamagnetic iron oxide （USPIO） are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction （AMI）.Methods An AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 107 magnetically labeled mesenchymal stem cells （MR-MSCs）. The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.Results MR-MSCs appeared as a local hypointense signal on T2 -weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T2 -weighted MRI, contrast to noise ratio （CNR） decreased in the MPIO-labeled group （16.07±5.85 vs. 10.96±1.34）and USPIO-labeled group （11.72±1.27 vs. 10.03±0.96） from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.Conclusions We demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability.USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.展开更多
基金Science Foundation of China （No. 30570743 and No. 30670853） and Pre-investigation Item of the Southeast University for Natural Science Foundation of China （No. XJ0590216）.
文摘Background Mesenchymal stem cells （MSCs） transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs （MR-MSCs） and monitor the restorative effects of MR-MSCs with magnetic resonance （MR） imaging. Methods Acute myocardial infarction （AMI） was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat （SPSS version 12.01）. Results A total of 26 swine were divided into four groups （sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7）. MSCs, MR-MSCs （10~cells） or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction （LVEF） was slightly increased in the AMI group （（41.87~2.45）% vs （39.04~2.80）%, P 〉0.05）, but significantly improved in the MR-MSCs group （（56.85~1.29）% vs （40.67~2.00）%, P 〈0.05） and unlabeled group （（55.38~1.07）% vs （41.78~2.08）%, P 〈0.05） at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Conclusion Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2- month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.
基金This work was supported by the grants from the National Natural Science Foundation of China （No. 30570743 and No. 30670853）, and Pre-investigation item of the Southeast University for National Natural Science Foundation of China （XJ0590216）.
文摘Background Superparamagnetic iron oxide （SPIO） particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging （MRI）. Micrometer-sized superparamagnetic iron oxide （MPIO）particles and nanometer-sized ultrasmall superparamagnetic iron oxide （USPIO） are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction （AMI）.Methods An AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 107 magnetically labeled mesenchymal stem cells （MR-MSCs）. The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.Results MR-MSCs appeared as a local hypointense signal on T2 -weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T2 -weighted MRI, contrast to noise ratio （CNR） decreased in the MPIO-labeled group （16.07±5.85 vs. 10.96±1.34）and USPIO-labeled group （11.72±1.27 vs. 10.03±0.96） from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.Conclusions We demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability.USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.
