Highly efficient magnetic labelling allows MRI tracking of the homing of stem cell‐derived extracellular vesicles following systemic delivery

Human stem‐cell‐derived extracellular vesicles (EVs) are currently being investigated for cell‐free therapy in regenerative medicine applications, but the lack of noninvasive imaging methods to track EV homing and uptake in injured tissues has limited the refinement and optimization of the approach....

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Bibliographic Details
Published in:Journal of extracellular vesicles 2021-01, Vol.10 (3), p.e12054-n/a
Main Authors: Han, Zheng, Liu, Senquan, Pei, Yigang, Ding, Zheng, Li, Yuguo, Wang, Xinge, Zhan, Daqian, Xia, Shuli, Driedonks, Tom, Witwer, Kenneth W., Weiss, Robert G., Zijl, Peter C.M., Bulte, Jeff W.M., Cheng, Linzhao, Liu, Guanshu
Format: Article
Language:English
Subjects:
acute kidney injury
Acute Kidney Injury - therapy
Animal models
Animals
Cell culture
Cell Culture Techniques
Cell- and Tissue-Based Therapy - methods
Disease Models, Animal
extracellular vesicle
Extracellular vesicles
Extracellular Vesicles - metabolism
Humans
Induced Pluripotent Stem Cells - metabolism
iPSC
Iron oxides
Labeling
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Metal Nanoparticles - therapeutic use
Mice
MRI
myocardial injury
Myocardial ischemia
Myocardial Ischemia - therapy
Nanoparticles
Peptides
Pluripotency
Polyhistidine
Regenerative medicine
Staining and Labeling - methods
stem cell
Stem cells
Tomography
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Summary:Human stem‐cell‐derived extracellular vesicles (EVs) are currently being investigated for cell‐free therapy in regenerative medicine applications, but the lack of noninvasive imaging methods to track EV homing and uptake in injured tissues has limited the refinement and optimization of the approach. Here, we developed a new labelling strategy to prepare magnetic EVs (magneto‐EVs) allowing sensitive yet specific MRI tracking of systemically injected therapeutic EVs. This new labelling strategy relies on the use of ‘sticky’ magnetic particles, namely superparamagnetic iron oxide (SPIO) nanoparticles coated with polyhistidine tags, to efficiently separate magneto‐EVs from unencapsulated SPIO particles. Using this method, we prepared pluripotent stem cell (iPSC)‐derived magneto‐EVs and subsequently used MRI to track their homing in different animal models of kidney injury and myocardial ischemia. Our results showed that iPSC‐derived EVs preferentially accumulated in the injury sites and conferred substantial protection. Our study paves a new pathway for preparing highly purified magnetic EVs and tracking them using MRI towards optimized, systemically administered EV‐based cell‐free therapies.
ISSN:2001-3078
2001-3078
DOI:10.1002/jev2.12054