Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model.
Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model.
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DOI：
10.1097/00029330-200803020-00016
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发表时间：
2008-03
影响因子：
6.1
通讯作者：
Chun-mei Qi;G. Ma;Nai-Feng Liu;Cheng-xing Shen;Zhong-pu Chen;Xiao-jun Liu;Yao-peng Hu;Xiao-li Zhang;G. Teng;S. Ju;Ming Ma;Y. Tang
中科院分区：
文献类型：
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作者：
Chun-mei Qi;G. Ma;Nai-Feng Liu;Cheng-xing Shen;Zhong-pu Chen;Xiao-jun Liu;Yao-peng Hu;Xiao-li Zhang;G. Teng;S. Ju;Ming Ma;Y. Tang
背景间充质干细胞（MSCs）移植为心肌修复提供了新的途径。然而，关于MSCs移植的许多重要的基本问题仍未得到解答。目前迫切需要从跳动的心脏中鉴定间充质干细胞，并分析这种新方法的有效性。本研究旨在定位磁标记间充质干细胞（MR-MSCs），并利用磁共振（MR）成像监测MR-MSCs的恢复作用。方法用球囊阻断猪左冠状动脉前降支，形成急性心肌梗死（AMI）。心肌梗死后冠脉内灌注细胞。3.0T MR扫描观察梗死面积变化及心功能变化。然后通过组织学和western blot分析证实结果。所有统计程序均采用Systat软件（SPSS 12.01版）进行。结果将26头猪分为4组（假手术组，n=6； AMI组合并PBS移植，n=6；标记MSCs组，n=7；未标记MSCs组，n=7）。在心肌梗死后，通过冠状动脉内注射MSCs、MR-MSCs（10(7)个细胞）或PBS，并在移植后0、4和8周进行一系列心脏MR成像研究。先生成像演示MI大小减少msc移植后在标签和标记组,然而,增加被认为在AMI组MI后8周。左心室射血分数(LVEF)略提高AMI组((41.87 + / - -2.45)% vs (39.04 + / - -2.80) %, P > 0.05),但显著提高MR-MSCs集团((56.85 + / - -1.29)% vs (40.67 + / - -2.00) %, P < 0.05)和无标号集团((55.38 + / - -1.07)% vs (41.78 + / - -2.08) %, P < 0.05),治疗后8周。普鲁士蓝染色和免疫荧光染色进一步证实MR-MSCs。Western blot分析显示，与AMI组和假手术组相比，MSCs处理组肌球蛋白重链、肌钙蛋白T等心肌细胞标志物表达增加，标记组和未标记组基质金属蛋白酶2与组织金属蛋白酶1的比值降低。结论移植MR-MSCs可在心肌梗死模型中再生新心肌，并在随访2个月后阻止心肌重塑，是未来临床研究更好地了解干细胞治疗机制的首选方法。
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(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. 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.