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Ioannides et al. J Cancer Metastasis Treat 2020;6:15 Journal of Cancer
DOI: 10.20517/2394-4722.2020.22 Metastasis and Treatment

Technical Note Open Access

Evaluating different routes of extracellular vesicle
administration for cranial therapies

Pericles Ioannides, Erich Giedzinski, Charles L. Limoli

Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.

Correspondence to: Dr. Charles L. Limoli, Department of Radiation Oncology, University of California, Irvine, CA 92617-2695,
USA. E-mail: climoli@uci.edu
How to cite this article: Ioannides P, Giedzinski E, Limoli CL. Evaluating different routes of extracellular vesicle administration for
cranial therapies. J Cancer Metastasis Treat 2020;6:15. http://dx.doi.org/10.20517/2394-4722.2020.22
Received: 9 Mar 2020 First Decision: 13 Apr 2020 Revised: 1 Jun 2020 Accepted: 5 Jun 2020 Published: 18 Jun 2020

Science Editor: Robert J. Griffin Copy Editor: Cai-Hong Wang Production Editor: Tian Zhang

Abstract
Aim: Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies
for the treatment of functionally compromised tissue beds and organ sites. Here we aimed to highlight multiple
administration routes for the potential treatment of various forms of brain injury.

Methods: Human neural stem cell-derived EV were isolated from conditioned media and administered via three
distinct routes: intrahippocampal transplantation, retro-orbital vein injection, and intranasal. EV were administered
after which brains were evaluated to determine the capability of EV to translocate into normal tissue.

Results: Data showed no significant differences in the amount of EV able to translocate across the brain, indicating
the functional equivalence of each administration route to effectively deliver EV to the brain parenchyma.

Conclusion: Findings show that both systemic administration routes (retro-orbital vein or intranasal delivery)
afforded effective penetrance and perfusion of EV throughout the brain in a minimally invasive manner, and point
to a translationally tractable option for treating certain neurological disorders including those resulting from cranial
irradiation procedures.

Keywords: Extracellular vesicles, cranial therapy, cognitive dysfunction

INTRODUCTION
Extracellular vesicles (EV) are secreted by nearly every mammalian cell type and contain a wealth of
bioactive cargo capable of modulating target cell function through a variety of paracrine signaling

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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