Imaging survival and function of transplanted cardiac resident stem cells.
Imaging survival and function of transplanted cardiac resident stem cells.
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DOI：
10.1016/j.jacc.2008.12.036
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发表时间：
2009-04-07
影响因子：
24
通讯作者：
Wu, Joseph C.
中科院分区：
文献类型：
--
作者：
Li, Zongjin;Lee, Andrew;Huang, Mei;Chun, Hyung;Chung, Jaehoon;Chu, Pauline;Hoyt, Grant;Yang, Phillip;Rosenberg, Jarrett;Robbins, Robert C.;Wu, Joseph C.
本研究的目的是通过分子影像学方法来鉴定驻留的心脏干细胞（CSCs）并研究其在心肌梗死中的治疗效果。CSC已经在体外分离和表征。这些细胞提供了一种刺激性的方法来再生受损的心肌。然而，移植CSC的生存动力学和功能尚未完全阐明。从组成型表达萤火虫荧光素酶（Fluc）和增强型绿色荧光蛋白（eGFP）报告基因的L2 G85转基因小鼠（FVB背景）中分离CSC。CSC在体外表征并在体内移植到鼠梗塞模型中。多模态无创成像技术被用来评估CSC的生存和治疗效果的心脏功能恢复。CSC可以从L2 G85小鼠中分离，并且FACS分析显示驻留CSC标志物（Sca-1，c-Kit）和间充质干细胞标志物（CD 90，CD 106）的表达。然后，将5×105个CSC（n=30）或PBS对照（n=15）注射到接受左前降支（LAD）结扎的同基因FVB小鼠的心脏中。生物发光成像（BLI）显示到第8周供体细胞存活较差。超声心动图、有创血流动力学压力-容积（PV）分析、氟-18-氟脱氧葡萄糖（[18 F]-FDG）正电子发射断层扫描（PET）成像和心脏磁共振成像（MRI）显示CSC组和对照组之间的心肌收缩力和活力无显著差异。最后，尸检分析证实移植的CSCs与宿主心肌细胞整合的免疫组织学。在小鼠心肌梗死（MI）模型中，Sca-1阳性CSC不提供长期植入，并且如通过多模态成像确定的对心脏功能有益。
The goal of this study is to characterize resident cardiac stem cells (CSCs) and investigate their therapeutic efficacy in myocardial infarction by molecular imaging methods. CSCs have been isolated and characterized in vitro. These cells offer a provocative method to regenerate the damaged myocardium. However, the survival kinetics and function of transplanted CSCs have not been fully elucidated. CSCs were isolated from L2G85 transgenic mice (FVB background) that constitutively express both firefly luciferase (Fluc) and enhanced green fluorescence protein (eGFP) reporter gene. CSCs were characterized in vitro and transplanted in vivo into murine infarction models. Multi-modality noninvasive imaging techniques were used to assess CSC survival and therapeutic efficacy for restoration of cardiac function. CSCs can be isolated from L2G85 mice and FACS analysis showed expression of resident CSCs markers (Sca-1, c-Kit) and mesenchymal stem cell markers (CD90, CD106). Afterwards, 5×105 CSCs (n=30) or PBS control (n=15) was injected into the hearts of syngeneic FVB mice undergoing left anterior descending artery (LAD) ligation. Bioluminescence imaging (BLI) showed poor donor cell survival by week 8. Echocardiogram, invasive hemodynamic pressure-volume (PV) analysis, positron emission tomography (PET) imaging with Fluorine-18-fluorodeoxyglucose ([18F]-FDG), and cardiac magnetic resonance imaging (MRI) demonstrated no significant difference in cardiac contractility and viability between the CSC and control group. Finally, postmortem analysis confirmed transplanted CSCs integrated with host cardiomyocytes by immunohistology. In a mouse myocardial infarction (MI) model, Sca-1 positive CSCs provide no long-term engraftment and benefit to cardiac function as determined by multi-modality imaging.
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影响因子：
37.8
作者：
Li, Zongjin;Wu, Jenny C.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
37.8
作者：
Cao, F;Lin, S;Wu, JC
通讯作者：
Wu, JC
影响因子：
15.9
作者：
Mclaughlin, L;Zhu, G;Aronow, BJ
通讯作者：
Aronow, BJ
影响因子：
37.8
作者：
Menasche, Philippe;Alfieri, Ottavio;Hagege, Albert A.
通讯作者：
Hagege, Albert A.
DOI：
10.1073/pnas.2637010100
发表时间：
2004-01-06
影响因子：
11.1
作者：
Cao, YA;Wagers, AJ;Contag, CH
通讯作者：
Contag, CH