Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium
Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium
复制标题
磁共振低血压信号主要来源于梗塞心肌移植间充质干细胞的长期追踪中的细胞外铁颗粒
DOI：
10.2147/ijn.s77858
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发表时间：
2015-03-02
影响因子：
8
通讯作者：
Ge J
中科院分区：
文献类型：
--
作者：
Huang Z;Li C;Yang S;Xu J;Shen Y;Xie X;Dai Y;Lu H;Gong H;Sun A;Qian J;Ge J
目的在长期的干细胞追踪过程中，心脏磁共振（CMR）的长期低信号被认为是由吞噬超顺磁性氧化铁（SPIO）的巨噬细胞引起的。然而，缺血心脏的铁清除能力是有限的。因此，我们推测细胞外SPIO颗粒也可能参与假阳性信号的产生。方法和结果将雄性猪间充质干细胞（MSCs）与SPIO孵育24小时，SPIO标记对细胞活力或分化均无显著影响。体外研究表明，磁共振不能区分SPIO与活的SPIO-MSC或死的SPIO-MSC。在建立雌性猪急性心肌梗死模型后2 h，将2×107只雄性SPIO标记的MSCs（n=5）或未标记的MSCs（n=5）经心外途径注入梗死心肌的10个不同部位。在体内CMR与T2星星加权成像-flash-2D序列显示了一个信号空对应于初始SPIO-MSC注射部位。移植后6个月，CMR确定了50个注射部位中的32个（64%），病理检查发现大量普鲁士蓝阳性铁沉积。然而，铁颗粒主要分布在细胞外间隙，少数分布在CD 68阳性巨噬细胞和其他CD 68阴性细胞内。未检测到供体MSCs性别决定区Y DNA。结论移植MSCs在心肌梗死后的长期追踪过程中，细胞外铁颗粒是导致CMR低信号的主要原因。应考虑到假阳性信号和心脏长期铁沉积的潜在心脏毒性。
Purpose The long-lasting hypointensities in cardiac magnetic resonance (CMR) were believed to originate from superparamagnetic iron oxide (SPIO)-engulfed macrophages during long-term stem cell tracking. However, the iron clearance capacity of the ischemic heart was limited. Therefore, we speculated that the extracellular SPIO particles may also be involved in the generation of false-positive signals. Methods and results Male swine mesenchymal stem cells (MSCs) were incubated with SPIO for 24 hours, and SPIO labeling had no significant effects on either cell viability or differentiation. In vitro studies showed that magnetic resonance failed to distinguish SPIO from living SPIO-MSCs or dead SPIO-MSCs. Two hours after the establishment of the female swine acute myocardial infarction model, 2×107 male SPIO-labeled MSCs (n=5) or unlabeled MSCs (n=5) were transextracardially injected into the infarcted myocardium at ten distinct sites. In vivo CMR with T2 star weighted imaging-flash-2D sequence revealed a signal void corresponding to the initial SPIO-MSC injection sites. At 6 months after transplantation, CMR identified 32 (64%) of the 50 injection sites, where massive Prussian blue-positive iron deposits were detected by pathological examination. However, iron particles were predominantly distributed in the extracellular space, and a minority was distributed within CD68-positive macrophages and other CD68-negative cells. No sex-determining region Y DNA of donor MSCs was detected. Conclusion CMR hypointensive signal is primarily caused by extracellular iron particles in the long-term tracking of transplanted MSCs after myocardial infarction. Consideration should be given to both the false-positive signal and the potential cardiac toxicity of long-standing iron deposits in the heart.