Imaging as a tool to accelerate the translation of extracellular vesicle‐based therapies for central nervous system diseases

Abstract

Extracellular vesicles (EVs) are natural and diverse lipid bilayer‐enclosed particles originating from various cellular components and containing an abundance of cargoes. Due to their unique properties, EVs have gained considerable interest as therapeutic agents for a variety of diseases, including central nervous system (CNS) disorders. Their therapeutic value depends on cell origin but can be further enhanced by enrichment of cargo when used as drug carriers. Therefore, there has been significant effort directed toward introducing them to clinical practice. However, it is essential to avoid the failures we have seen with whole‐cell therapy, in particular for the treatment of the CNS. Successful launching of clinical studies is contingent upon the understanding of the biodistribution of EVs, including their uptake and clearance from organs and specific homing into the region of interest. A multitude of noninvasive imaging methods has been explored in vitro to investigate the spatio‐temporal dynamics of EVs administered in vivo. However, only a few studies have been performed to track the delivery of EVs, especially delivery to the brain, which is the most therapeutically challenging organ. We focus here on the use of advanced imaging techniques as an essential tool to facilitate the acceleration of clinical translation of EV‐based therapeutics, especially in the CNS arena. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging

Non‐Invasive imaging of extracellular vesicles: Quo vaditis in vivo?

“…Despite the myriad demonstrated, assumed, and posited benefits of EVs or NVs, much remains unknown about the fate of these vesicles in vivo once administered (Chuo et al., 2018 ; Di Rocco et al., 2016 ; Gangadaran et al., 2017 ; Gao et al., 2021 ). The major questions to be addressed are: Quo vaditis (where are you/they going)?…”

Mesenchymal Stem Cells Do Not Lose Direct Labels Including Iron Oxide Nanoparticles and DFO-89Zr Chelates through Secretion of Extracellular Vesicles

“…Notably, the current study has different implications related to the administration of EVs themselves as therapeutic agents. The possibility of imaging and monitoring EV administration is equally important in the case of stem cells in order to better understand their therapeutic potential and the fate of EVs, as well as to accelerate the translation of extracellular vesicle-based therapies [ 15 ]. Thus, a reliable method for in vivo noninvasive assessment of administrated EVs is highly desirable.…”

Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy – A Comprehensive Literature Review

“…These include optical (bioluminescent imaging (BLI) and fluorescence imaging are its primary forms), tomographical (CT and MRI), nuclear imaging modalities (Radioactive substances), and photoacoustic imaging. 125 , 126 Imaging technologies provide numerous advantages, including high sensitivity, perfect spatiotemporal precision, the ability to penetrate deep into tissues, superior resolution, and remarkable tissue contrasts. 127 NSC-sEVs have a wide range of therapeutic potential, and numerous tracking methods have been designed to investigate how they work.…”