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The long-term fate of mesenchymal stem cells labeled with magnetic resonance imaging-visible polymersomes in cerebral ischemia

Authors Duan X, Lu L, Wang Y, Zhang F, Mao J, Cao M, Lin B, Zhang X, Shuai X, Shen J

Received 19 July 2017

Accepted for publication 16 August 2017

Published 8 September 2017 Volume 2017:12 Pages 6705—6719

DOI https://doi.org/10.2147/IJN.S146742

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Professor Dongwoo Khang


Xiaohui Duan,1,* Liejing Lu,1,* Yong Wang,2 Fang Zhang,1 Jiaji Mao,1 Minghui Cao,1 Bingling Lin,1 Xiang Zhang,1 Xintao Shuai,2,3 Jun Shen1

1Department of Radiology, Sun Yat-Sen Memorial Hospital, 2PCFM Lab of Ministry of Education, School of Materials Science and Engineering, 3BME Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Abstract: Understanding the long-term fate and potential mechanisms of mesenchymal stem cells (MSCs) after transplantation is essential for improving functional benefits of stem cell-based stroke treatment. Magnetic resonance imaging (MRI) is considered an attractive and clinically translatable tool for longitudinal tracking of stem cells, but certain controversies have arisen in this regard. In this study, we used SPION-loaded cationic polymersomes to label green fluorescent protein (GFP)-expressing MSCs to determine whether MRI can accurately reflect survival, long-term fate, and potential mechanisms of MSCs in ischemic stroke therapy. Our results showed that MSCs could improve the functional outcome and reduce the infarct volume of stroke in the brain. In vivo MRI can verify the biodistribution and migration of grafted cells when pre-labeled with SPION-loaded polymersome. The dynamic change of low signal volume on MRI can reflect the tendency of cell survival and apoptosis, but may overestimate long-term survival owing to the presence of iron-laden macrophages around cell graft. Only a small fraction of grafted cells survived up to 8 weeks after transplantation. A minority of these surviving cells were differentiated into astrocytes, but not into neurons. MSCs might exert their therapeutic effect via secreting paracrine factors rather than directing cell replacement through differentiation into neuronal and/or glial phenotypes.

Keywords: mesenchymal stem cells, magnetic resonance imaging, superparamagnetic iron oxide nanoparticles, polymersome, ischemic stroke, green fluorescence protein

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