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bioRxiv · 10.1101/2025.03.02.641040

Magnetically Labeled iPSC-Derived Extracellular Vesicles Enable MRI/MPI-Guided Regenerative Therapy for Myocardial Infarction

Wang, W.·Han, Z.·Aafreen, S.·Zivko, C.·Gololobova, O.·Wei, Z.·Cotin, G.·Felder-Flesch, D.·Mahairaki, V.·Witwer, K. W.·Bulte, J. W. M.·Weiss, R. G.·Liu, G.
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Abstract

Stem cell-derived extracellular vesicles (EVs) offer a promising cell-free approach for cardiovascular regenerative medicine. In this study, we developed magnetically labeled induced pluripotent stem cell-derived EVs (magneto-iPSC-EVs) encapsulated with superparamagnetic iron oxide (SPIO) nanoparticles for image-guided regenerative treatment of myocardial infarction, in which EVs that can be detected by both magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). iPSC-EVs were isolated, characterized per MISEV2023 guidelines, and loaded with SuperSPIO20 nanoparticles using optimized electroporation conditions (300 V, 2 x 10 ms pulses), achieving a high loading efficiency of 1.77 ng Fe/106 EVs. In vitro results show that magneto-iPSC-EVs can be sensitively detected by MPI and MRI, with a detectability of approximately 107 EVs. In a mouse myocardial ischemia-reperfusion model, intramyocardially injected magneto-iPSC-EVs (2 x 109) were imaged non-invasively by in vivo MPI for 7 days and ex vivo MRI, with the presence of magneto-iPSC-EVs confirmed by Prussian blue staining. Therapeutically, both native and magneto-iPSC-EVs significantly improved cardiac function, with a 37.3% increase in left ventricular ejection fraction and 61.0% reduction in scar size. This study highlights the potential of magneto-iPSC-EVs as a cell-free approach for cardiovascular regenerative medicine, offering both non-invasive imaging capabilities and therapeutic benefits for myocardial repair.

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Wang, W., Han, Z., Aafreen, S., Zivko, C., Gololobova, O., Wei, Z., Cotin, G., Felder-Flesch, D., Mahairaki, V., Witwer, K. W., Bulte, J. W. M., Weiss, R. G., Liu, G.. 2025-03-10. Magnetically Labeled iPSC-Derived Extracellular Vesicles Enable MRI/MPI-Guided Regenerative Therapy for Myocardial Infarction. https://doi.org/10.1101/2025.03.02.641040

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