Noninvasive monitoring of oxidative stress in transplanted mesenchymal stromal cells.
Noninvasive monitoring of oxidative stress in transplanted mesenchymal stromal cells.
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DOI：
10.1016/j.jcmg.2012.11.018
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发表时间：
2013-07
影响因子：
14
通讯作者：
Rodriguez-Porcel, Martin
中科院分区：
文献类型：
--
作者：
Psaltis, Peter J.;Peterson, Karen M.;Xu, Rende;Franchi, Federico;Witt, Tyra;Chen, Ian Y.;Lerman, Amir;Simari, Robert D.;Gambhir, Sanjiv S.;Rodriguez-Porcel, Martin
我们旨在验证一种通路特异性报告基因，该基因可用于对祖细胞的氧化状态进行无创成像。在细胞治疗研究中，报告基因成像在评估活体细胞命运方面发挥着重要作用。心肌损伤后，宿主组织中的有害刺激会给移植细胞带来氧化应激，从而影响其存活和修复功能。研究了大鼠间充质间质细胞（MSCs）在体外应激下氧化应激增加的表型证据。基于它们对促氧化酶NAD(P)H氧化酶p67phox的上调，构建了由NAD(P)H p67phox启动子驱动的萤火虫荧光素酶（Fluc）报告基因组成的氧化应激传感器。在体外和体内促氧化条件下，研究了NAD(P)H p67phox-Fluc和细胞活力报告基因（CMV-Renilla荧光素酶）共转染的MSCs。在低血清培养过程中对传感器进行体外验证后，将转染的MSCs移植到大鼠心肌缺血/再灌注（IR）模型中，并进行生物发光成像监测。与假对照（无IR）相比，IR大鼠心脏Fluc强度显著升高（6 h 3.5倍，24 h 2.6倍，48 h 5.4倍，P<0.01），表明细胞氧化应激增加。校正肾荧光素酶（Rluc）活性后的离体光度法证实了这一点，Rluc活性是衡量活MSC数量的指标（48 h时，假手术Fluc:Rluc比值为0.011±0.003，IR为0.026±0.004，P<0.05）。此外，在接受抗氧化剂（tempol）预处理的MSCs的IR动物中，Fluc信号被强烈减弱，证实了氧化应激传感器的特异性。通路特异性报告基因成像可以评估MSCs输送到缺血心肌后氧化状态的变化，为监测活体移植细胞与其宿主环境之间的关键生物相互作用提供模板。
We aimed to validate a pathway-specific reporter gene that could be used to noninvasively image the oxidative status of progenitor cells. In cell therapy studies, reporter gene imaging plays a valuable role in the assessment of cell fate in living subjects. After myocardial injury, noxious stimuli in the host tissue confer oxidative stress to transplanted cells that may influence their survival and reparative function. Rat mesenchymal stromal cells (MSCs) were studied for phenotypic evidence of increased oxidative stress under in vitro stress. On the basis of their upregulation of the pro-oxidant enzyme NAD(P)H oxidase p67phox, an oxidative stress sensor was constructed, comprising the firefly luciferase (Fluc) reporter gene driven by the NAD(P)H p67phox promoter. MSCs co-transfected with NAD(P)H p67phox-Fluc and a cell viability reporter gene (CMV-Renilla luciferase) were studied under in vitro and in vivo pro-oxidant conditions. After in vitro validation of the sensor during low serum culture, transfected MSCs were transplanted into a rat model of myocardial ischemia/reperfusion (IR) and monitored by bioluminescence imaging. Compared to sham controls (no IR), cardiac Fluc intensity was significantly higher in IR rats (3.5-fold at 6 h, 2.6-fold at 24 h, 5.4-fold at 48 h, P<0.01), indicating increased cellular oxidative stress. This was corroborated by ex vivo luminometry after correcting for renilla luciferase (Rluc) activity as a measure of viable MSC number (Fluc:Rluc ratio 0.011 ± 0.003 for sham versus 0.026 ± 0.004 for IR at 48 h, P<0.05). Furthermore, in IR animals that received MSCs preconditioned with an anti-oxidant agent (tempol), Fluc signal was strongly attenuated, substantiating the specificity of the oxidative stress sensor. Pathway-specific reporter gene imaging allows assessment of changes in the oxidative status of MSCs after delivery to ischemic myocardium, providing a template to monitor key biological interactions between transplanted cells and their host environment in living subjects.
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骨髓干细胞移植到缺血心肌后的体内功能和转录谱。
DOI：
10.1161/atvbaha.111.238618
发表时间：
2012-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Sheikh AY;Huber BC;Narsinh KH;Spin JM;van der Bogt K;de Almeida PE;Ransohoff KJ;Kraft DL;Fajardo G;Ardigo D;Ransohoff J;Bernstein D;Fischbein MP;Robbins RC;Wu JC
通讯作者：
Wu JC
影响因子：
5.2
作者：
Wang, Xiaohong;Zhao, Tiemin;Huang, Wei;Wang, Tao;Qian, Jiang;Xu, Meifeng;Kranias, Evangelia G.;Wang, Yigang;Fan, Guo-Chang
通讯作者：
Fan, Guo-Chang
影响因子：
48
作者：
Loening, Andreas Markus;Wu, Anna M.;Gambhir, Sanjiv Sam
通讯作者：
Gambhir, Sanjiv Sam
DOI：
10.1161/circimaging.108.797449
发表时间：
2008-09
期刊：
Circulation. Cardiovascular imaging
影响因子：
--
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
通讯作者：
Glogar D
影响因子：
3.7
作者：
Brandl, Anita;Meyer, Matthias;Angele, Peter
通讯作者：
Angele, Peter