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使用超顺磁性氧化铁的磁共振成像无法追踪移植到心脏中的间充质干细胞的长期命运。

Magnetic resonance imaging with superparamagnetic iron oxide fails to track the long-term fate of mesenchymal stem cells transplanted into heart.

作者信息

Ma Ning, Cheng Huaibing, Lu Minjie, Liu Qiong, Chen Xiuyu, Yin Gang, Zhu Hao, Zhang Lianfeng, Meng Xianmin, Tang Yue, Zhao Shihua

机构信息

Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College.

Comparative Medical Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS).

出版信息

Sci Rep. 2015 Mar 12;5:9058. doi: 10.1038/srep09058.

Abstract

MRI for in vivo stem cell tracking remains controversial. Here we tested the hypothesis that MRI can track the long-term fate of the superparamagnetic iron oxide (SPIO) nanoparticles labelled mesenchymal stem cells (MSCs) following intramyocardially injection in AMI rats. MSCs (1 × 10(6)) from male rats doubly labeled with SPIO and DAPI were injected 2 weeks after myocardial infarction. The control group received cell-free media injection. In vivo serial MRI was performed at 24 hours before cell delivery (baseline), 3 days, 1, 2, and 4 weeks after cell delivery, respectively. Serial follow-up MRI demonstrated large persistent intramyocardial signal-voids representing SPIO during the follow-up of 4 weeks, and MSCs did not moderate the left ventricular dysfunction. The TUNEL analysis confirmed that MSCs engrafted underwent apoptosis. The histopathological studies revealed that the site of cell injection was infiltrated by inflammatory cells progressively and the iron-positive cells were macrophages identified by CD68 staining, but very few or no DAPI-positive stem cells at 4 weeks after cells transplantation. The presence of engrafted cells was confirmed by real-time PCR, which showed that the amount of Y-chromosome-specific SRY gene was consistent with the results. MRI may not reliably track the long-term fate of SPIO-labeled MSCs engraftment in heart.

摘要

用于体内干细胞追踪的磁共振成像(MRI)仍存在争议。在此,我们验证了一个假设,即MRI能够追踪超顺磁性氧化铁(SPIO)纳米颗粒标记的间充质干细胞(MSCs)在急性心肌梗死(AMI)大鼠心肌内注射后的长期命运。将来自雄性大鼠的经SPIO和4',6-二脒基-2-苯基吲哚(DAPI)双重标记的MSCs(1×10⁶个)在心肌梗死后2周进行注射。对照组接受无细胞培养基注射。分别在细胞递送前24小时(基线)、细胞递送后3天、1周、2周和4周进行体内连续MRI检查。连续的随访MRI显示,在4周的随访期间,代表SPIO的心肌内大的持续性信号缺失,并且MSCs并未改善左心室功能障碍。TUNEL分析证实植入的MSCs发生了凋亡。组织病理学研究显示,细胞注射部位逐渐被炎性细胞浸润,经CD68染色鉴定铁阳性细胞为巨噬细胞,但在细胞移植后4周时极少或没有DAPI阳性干细胞。通过实时聚合酶链反应(PCR)证实了植入细胞的存在,其显示Y染色体特异性性别决定区Y基因(SRY)的量与结果一致。MRI可能无法可靠地追踪SPIO标记的MSCs在心脏中植入的长期命运。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04b8/4356978/f64a94c5ccab/srep09058-f1.jpg

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