锰增强磁共振成像可在猪缺血再灌注模型中对干细胞治疗后梗死周围组织恢复情况进行体内确认。
Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model.
作者信息
Dash Rajesh, Kim Paul J, Matsuura Yuka, Ikeno Fumiaki, Metzler Scott, Huang Ngan F, Lyons Jennifer K, Nguyen Patricia K, Ge Xiaohu, Foo Cheryl Wong Po, McConnell Michael V, Wu Joseph C, Yeung Alan C, Harnish Phillip, Yang Phillip C
机构信息
Division of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.) Stanford Cardiovascular Institute, Stanford University, Stanford, CA (R.D., N.F.H., P.K.N., M.V.M.C., J.C.W., P.C.Y.).
Division of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
出版信息
J Am Heart Assoc. 2015 Jul 27;4(7):e002044. doi: 10.1161/JAHA.115.002044.
BACKGROUND
The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts.
METHODS AND RESULTS
Twelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05).
CONCLUSIONS
The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells.
背景
干细胞疗法增强缺血性心肌病功能的确切机制尚不清楚。在本研究中，我们假设梗死周边区域（PIR）活力增加会在干细胞植入后产生恢复性益处。一种新型多模态成像方法同时评估了损伤猪心脏的心肌活力（锰增强磁共振成像[MEMRI]）、心肌瘢痕（延迟钆增强磁共振成像）和移植干细胞植入情况（正电子发射断层扫描报告基因）。
方法与结果
12只成年猪接受了缺血再灌注损伤。通过延迟钆增强磁共振成像阳性心肌（PIR和梗死灶内区域）减去MEMRI阴性心肌（梗死灶内区域）进行数字减法，清晰地勾勒出了PIR，其中MEMRI阳性信号反映了PIR活力。人羊膜间充质干细胞（hAMSCs）是一种独特的具有免疫调节作用的中胚层干细胞群体，可恢复小鼠的PIR。hAMSC递送后立即进行的MEMRI显示，与对照组相比，PIR活力信号增加。在接受hAMSC治疗的心脏中，直接的PIR活力在超过6周的时间内一直保持较高水平。免疫细胞化学证实，PIR活力增加与区域收缩力改善、左心室射血分数、梗死面积以及hAMSC植入相关。梗死灶内区域和PIR中MEMRI和正电子发射断层扫描报告基因信号增加与hAMSC组内持续的功能增强（整体和区域）相关（平均变化，左心室射血分数：hAMSC组为85±60%，对照组为8±10%；P<0.05），且心室扩张减少（左心室舒张末期容积增加：hAMSC组为24±8%，对照组为110±30%；P<0.05）。
结论
hAMSC植入的正电子发射断层扫描报告基因信号与PIR中改善的MEMRI信号相关。增加的MEMRI信号代表PIR活力以及受损心脏的恢复潜力。这种体内多模态成像平台代表了一种新颖的实时跟踪PIR活力和干细胞植入的方法，同时为心血管干细胞的治疗效果提供了机制解释。
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