Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure
Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure
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多模态成像用于小鼠心力衰竭模型中诱导多能干细胞的体内评估
DOI：
10.1111/aor.12728
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发表时间：
2016
影响因子：
2.4
通讯作者：
Martens A
中科院分区：
文献类型：
--
作者：
Rojas SV;Meier M;Zweigerdt R;Eckardt D;Rathert C;Schecker N;Schmitto JD;Rojas- Hernandez S;Martin U;Kutschka I;Haverich A;Martens A
心肌干细胞治疗心力衰竭强烈依赖于成功的细胞移植、移植和存活。此外，通常在心肌内注射后直接观察到大量细胞损失，因此需要对移植细胞进行有效的纵向监测，以开发更有效的移植技术。因此，本研究的目的是利用体内生物发光分析（BLI）和磁共振成像（MRI）来评估心肌内移植后诱导多能干细胞的活力和心脏保留。转染小鼠诱导多能干细胞（iPSCs）表达荧光素酶报告基因，并用超顺磁性氧化铁颗粒在细胞内进行标记。因此，在小鼠左冠状动脉前降支结扎后，将5 × 105个细胞移植到心内。在14天的随访中，使用BLI和序列T2*序列MRI检测心脏iPSCs。此外，通过MRI评估梗死范围和左室（LV）功能。对照组接受相同的手术，但没有注射细胞。MRI序列显示，标记的iPSCs与心肌晚期增强相关，MRI信号强烈，表明植入梗死区。在第0天，平均iPSC体积为4.2±0.4 mm3；3.1±0.4 mm3at第7天；2周后为5.1±0.8 mm3。注射后胸部BLI亮度从1.0 × 106±4.2 × 104（p/s/cm2/sr）直接下降到第1天的1.0 × 105±4.9 × 103（p/s/cm2/sr）。注射后2周，BLI亮度增加到1.1 × 106±4.2 × 104（p/s/cm2/sr）。通过离体BLI分析和组织学证实了心脏移植的定位。iPSC组左室射血分数（30.9±0.9%）高于梗死对照组（24.0±2.1%，P< 0.05）。MRI和BLI联合评估干细胞在体内的命运，使心脏移植定位与评估心肌梗死时的左室功能成为可能。
Myocardial stem cell therapy in heart failure is strongly dependent on successful cellular transfer, engraftment, and survival. Moreover, massive cell loss directly after intramyocardial injection is commonly observed, generating the need for efficient longitudinal monitoring of transplanted cells in order to develop more efficient transplantation techniques. Therefore, the aim of the present study was to assess viability and cardiac retention of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis (BLI) and magnetic resonance imaging (MRI). Murine induced pluripotent stem cells (iPSCs) were transfected for luciferase reporter gene expression and labeled intracellularly with supraparamagnetic iron oxide particles. Consequently, 5 × 105cells were transplanted intramyocardially following left anterior descending coronary artery ligation in mice. Cardiac iPSCs were detected using BLI and serial T2* sequences by MRI in a 14‐day follow‐up. Additionally, infarct extension and left ventricular (LV) function were assessed by MRI. Controls received the same surgical procedure without cell injection. MRI sequences showed a strong MRI signal of labeled iPSCs correlating with myocardial late enhancement, demonstrating engraftment in the infarcted area. Mean iPSC volumes were 4.2 ± 0.4 mm3at Day 0; 3.1 ± 0.4 mm3at Day 7; and 5.1 ± 0.8 mm3after 2 weeks. Thoracic BLI radiance decreased directly after injection from 1.0 × 106± 4.2 × 104(p/s/cm2/sr) to 1.0 × 105± 4.9 × 103(p/s/cm2/sr) on Day 1. Afterward, BLI radiance increased to 1.1 × 106± 4.2 × 104(p/s/cm2/sr) 2 weeks after injection. Cardiac graft localization was confirmed by ex vivo BLI analysis and histology. Left ventricular ejection fraction was higher in the iPSC group (30.9 ± 0.9%) compared to infarct controls (24.0 ± 2.1%;P< 0.05). The combination of MRI and BLI assesses stem cell fate in vivo, enabling cardiac graft localization with evaluation of LV function in myocardial infarction.
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影响因子：
3.4
作者：
T. Kofidis;D. Lebl;R. Swijnenburg;Joan M. Greeve;U. Klima;R. Robbins
通讯作者：
R. Robbins
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影响因子：
37.8
作者：
Yang,PhillipC
通讯作者：
Yang,PhillipC
影响因子：
14
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
通讯作者：
Rodriguez-Porcel, Martin
双模态生物发光和 MRI 在监测干细胞存活和对心肌梗死后重塑的影响中的应用。
影响因子：
4.8
作者：
Zhang,Hualei;Qiao,Hui;Bakken,Ashley;Gao,Fabao;Huang,Bin;Liu,YingqiuY;El-Deiry,Wafik;Ferrari,VictorA;Zhou,Rong
通讯作者：
Zhou,Rong
影响因子：
3.7
作者：
Martens A;Rojas SV;Baraki H;Rathert C;Schecker N;Hernandez SR;Schwanke K;Zweigerdt R;Martin U;Saito S;Haverich A;Kutschka I
通讯作者：
Kutschka I