Qi Chun-mei, Ma Gen-shan, Liu Nai-feng, Shen Cheng-xing, Chen Zhong, Liu Xiao-jun, Hu Yao-peng, Zhang Xiao-li, Teng Gao-jun, Ju Sheng-hong, Ma Ming, Tang Yao-liang
Department of Cardiolvascular Research Center, Zhongda Hospital, Southeast University, Nangjing, Jiangsu 210009, China.
Chin Med J (Engl). 2008 Mar 20;121(6):544-50.
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.
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).
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(7) 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.
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.
间充质干细胞（MSCs）移植为心肌修复提供了一种新方法。然而，关于MSCs移植的许多重要基本问题仍未得到解答。迫切需要从跳动的心脏中识别出MSCs，并分析这种新方法的疗效。本研究旨在通过磁共振（MR）成像定位磁性标记的MSCs（MR-MSCs）并监测其修复效果。
通过球囊闭塞左前降支冠状动脉在猪身上制造急性心肌梗死（AMI）。心肌梗死后通过冠状动脉内输注递送细胞。使用3.0T MR扫描仪评估梗死面积变化和心脏功能。然后通过组织学和蛋白质印迹分析确认结果。所有统计程序均使用Systat（SPSS版本12.01）进行。
总共26头猪分为四组（假手术组，n = 6；PBS移植的AMI组，n = 6；标记的MSCs组，n = 7；未标记的MSCs组，n = 7）。心肌梗死后通过冠状动脉内注射递送MSCs、MR-MSCs（10⁷个细胞）或PBS，并在移植后0、4和8周进行系列心脏MR成像研究。MR成像显示标记组和未标记组MSCs移植后MI面积减小，但AMI组在心肌梗死后8周面积增加。AMI组左心室射血分数（LVEF）略有增加（（41.87±2.45）%对（39.04±2.80）%，P>0.05），但在治疗后8周，MR-MSCs组（（56.85±1.29）%对（40.67±2.00）%，P<0.05）和未标记组（（55.38±1.07）%对（41.78±2.08）%，P<0.05）显著改善。通过普鲁士蓝和免疫荧光染色进一步证实了MR-MSCs。蛋白质印迹分析表明，与AMI组和假手术组相比，MSCs治疗组中心肌细胞标志物如肌球蛋白重链和肌钙蛋白T的表达增加，标记组和未标记组中基质金属蛋白酶2与金属蛋白酶组织抑制剂1的比率降低。
在2个月的随访中，移植的MR-MSCs可在MI模型中再生新的心肌并防止重塑，代表了一种在未来临床研究中更好地理解干细胞治疗机制的优选方法。
