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

Zheng Han, Senquan Liu, Yigang Pei, Zheng Ding, Yuguo Li, Xinge Wang, Daqian Zhan, Shuli Xia, Tom Driedonks, Kenneth W. Witwer, Robert G. Weiss, Peter C.M. van Zijl, Jeff W.M. Bulte, Linzhao Cheng, Guanshu Liu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere12054
JournalJournal of Extracellular Vesicles
Volume10
Issue number3
DOIs
StatePublished - Jan 2021

Keywords

  • MRI
  • acute kidney injury
  • extracellular vesicle
  • iPSC
  • myocardial injury
  • stem cell

ASJC Scopus subject areas

  • Histology
  • Cell Biology

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