Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression.
Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression.
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DOI：
10.1161/circimaging.108.797449
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发表时间：
2008-09
期刊：
影响因子：
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通讯作者：
Glogar D
中科院分区：
文献类型：
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作者：
Gyöngyösi M;Blanco J;Marian T;Trón L;Petneházy O;Petrasi Z;Hemetsberger R;Rodriguez J;Font G;Pavo IJ;Kertész I;Balkay L;Pavo N;Posa A;Emri M;Galuska L;Kraitchman DL;Wojta J;Huber K;Glogar D
用慢病毒载体稳定转染猪骨髓间充质干细胞（MSCs），用于转基因表达融合蛋白肾荧光素酶、红色荧光蛋白和单纯疱疹截断胸苷激酶（LV-RL-RFP-tTK；正电子发射断层扫描[PET]报告基因），以在体内无创跟踪心肌内传递的MSC命运。在农场猪中建立了闭胸再灌注心肌梗死。心肌梗死后16天，在梗死边界区使用机电定位引导，在心肌内注射LV-RL-RFP-tTK-MSCs （n=7）。在LV-RL-RFP-tTK-MSC治疗后30±2小时和7天，静脉注射10 mCi [18F]-FHBG和13n -氨PET后进行PET计算机断层代谢和灌注成像。使用[18F]-FHBG pet计算机断层扫描与MRI融合成像来确定注射的LV-RL-RFP-tTK-MSCs的心肌位置。注射后7天，[18F]-FHBG PET显示治疗动物心脏摄取减少，心包和胸膜摄取轻度增加，荧光素酶活性测定证实了这一点。第10天，lv - rl - rfp - ttk - msc治疗动物的MRI梗死面积小于对照组（n=7）（23.3±1.5%比30.2±3.5%，P<0.005）。心肌内分娩10 d后心肌组织组织学证实LV-RL-RFP-tTK-MSCs的存在（占注射细胞的5.8±1.1%）。报告基因成像能够在分娩后10天使用临床PET扫描仪跟踪存活的LV-RL-RFP-tTK-MSC在梗死周围猪心肌中的持久性。
Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, red fluorescent protein and herpes simplex truncated thymidine kinase (LV-RL-RFP-tTK; positron emission tomography [PET] reporter gene) for in vivo noninvasive tracking of the intramyocardially delivered MSC fate. A closed-chest, reperfused myocardial infarction was created in farm pigs. Sixteen days after myocardial infarction, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic metabolic and perfusion imaging was performed after an intravenous injection of 10 mCi [18F]-FHBG and 13N–ammonia PET at 30±2 hours and 7 days after LV-RL-RFP-tTK-MSC treatment. Fusion imaging of the [18F]-FHBG PET-computed tomography with MRI was used to determine the myocardial location of the injected LV-RL-RFP-tTK-MSCs. Seven days after injections, [18F]-FHBG PET showed a decreased cardiac uptake with a mild increased pericardial and pleura uptake in the treated animals, which was confirmed by the measurement of luciferase activity. At 10 days, infarct size by MRI in the LV-RL-RFP-tTK-MSC-treated animals was smaller than controls (n=7) (23.3±1.5% versus 30.2±3.5%, P<0.005). The presence of the LV-RL-RFP-tTK-MSCs (5.8±1.1% of the injected cells) in the myocardium 10 days after intramyocardial delivery was confirmed histologically. Reporter gene imaging enables the tracking of the persistence of viable LV-RL-RFP-tTK-MSC in the peri-infarcted porcine myocardium at 10 days after delivery using clinical PET scanners.