Ferritin Overexpression for Noninvasive Magnetic Resonance Imaging-Based Tracking of Stem Cells Transplanted into the Heart
Ferritin Overexpression for Noninvasive Magnetic Resonance Imaging-Based Tracking of Stem Cells Transplanted into the Heart
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DOI：
10.2310/7290.2010.00020
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发表时间：
2010-07-01
影响因子：
2.8
通讯作者：
Murry, Charles E.
中科院分区：
文献类型：
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作者：
Naumova, Anna V.;Reinecke, Hans;Murry, Charles E.
心脏细胞治疗中未满足的需求是一种非侵入性成像技术，能够跟踪移植物尺寸随时间的变化并监测细胞动力学，如复制和死亡，常用的超顺磁性纳米颗粒对这些因素不敏感。我们的目标是探索铁蛋白（一种无毒的铁结合蛋白）的过度表达是否可以用于移植到梗死心脏的细胞的非侵入性磁共振成像（MRI）。小鼠骨骼肌成肌细胞（C2 C12细胞）被改造为过表达铁蛋白。铁蛋白过表达不干扰细胞活力，增殖，或分化成多核肌管。与野生型细胞相比，铁蛋白过表达导致体外T-2弛豫时间减少25%。转基因移植物在移植到同系小鼠的梗死心脏后3周在体内检测到由过表达的铁蛋白复合物中的铁积累引起的低信号区。通过MRI评估的移植物尺寸与组织学测量结果密切相关（R-2 = .8）。我们的研究证明了铁蛋白在小鼠骨骼肌成肌细胞中过表达的可行性，以及在移植到梗死小鼠心脏后通过MRI在体外和体内成功检测转基因细胞。这些实验为使用MRI基因报告铁蛋白来追踪移植到心脏的干细胞奠定了基础。
An unmet need in cardiac cell therapy is a noninvasive imaging technique capable of tracking changes in graft size over time and monitoring cell dynamics such as replication and death, factors to which commonly used superparamagnetic nanoparticles are insensitive. Our goal was to explore if overexpression of ferritin, a nontoxic iron-binding protein, can be used for noninvasive magnetic resonance imaging (MRI) of cells transplanted into the infarcted heart. Mouse skeletal myoblasts (C2C12 cells) were engineered to overexpress ferritin. Ferritin overexpression did not interfere with cell viability, proliferation, or differentiation into multinucleated myotubes. Ferritin overexpression caused a 25% decrease in T-2 relaxation time in vitro compared to wild-type cells. Transgenic grafts were detected in vivo 3 weeks after transplantation into infarcted hearts of syngeneic mice as areas of hypointensity caused by iron accumulation in overexpressed ferritin complexes. Graft size evaluation by MRI correlated tighly with histologic measurements (R-2 = .8). Our studies demonstrated the feasibility of ferritin overexpression in mouse skeletal myoblasts and the successful detection of transgenic cells by MRI in vitro and in vivo after transplantation into the infarcted mouse heart. These experiments lay the groundwork for using the MRI gene reporter ferritin to track stem cells transplanted to the heart.