Magnetic Resonance Imaging with Superparamagnetic Iron Oxide Fails to Track the Long-term Fate of Mesenchymal Stem Cells Transplanted into Heart

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作者
Ning Ma
Huaibing Cheng
Minjie Lu
Qiong Liu
Xiuyu Chen
Gang Yin
Hao Zhu
Lianfeng Zhang
Xianmin Meng
Yue Tang
Shihua Zhao
机构
[1] State Key Laboratory of Cardiovascular Disease,Department of Radiology
[2] Fuwai Hospital,Department of Cardiology, Beijing Anzhen Hospital
[3] National Center for Cardiovascular Diseases,Arrhythmia Diagnosis and Treatment Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital
[4] Chinese Academy of Medical Sciences and Peking Union Medical College,undefined
[5] Comparative Medical Center,undefined
[6] Peking Union Medical College (PUMC) and Institute of Laboratory Animal Science,undefined
[7] Chinese Academy of Medical Science (CAMS),undefined
[8] Core Laboratory,undefined
[9] State Key Laboratory of Cardiovascular Disease,undefined
[10] Fuwai Hospital,undefined
[11] National Center for Cardiovascular Diseases,undefined
[12] Chinese Academy of Medical Sciences and Peking Union Medical College,undefined
[13] Experimental Animal Center,undefined
[14] State Key Laboratory of Cardiovascular Disease,undefined
[15] Fuwai Hospital,undefined
[16] National Center for Cardiovascular Diseases,undefined
[17] Chinese Academy of Medical Sciences and Peking Union Medical College,undefined
[18] Capital Medical University,undefined
[19] Beijing Institute of Heart Lung and Blood Vessel Diseases,undefined
[20] National Center for Cardiovascular Diseases,undefined
[21] Chinese Academy of Medical Sciences and Peking Union Medical College,undefined
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摘要
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 × 106) 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.
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