Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting

By O. Wiklander, J. Nordin, Aisling J O'Loughlin, Y. Gustafsson, Giulia Corso, Imre Mäger, P. Vader, Y. Lee, Helena Sork, Y. Seow and 8 more. Journal of Extracellular Vesicles, 2015

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Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in a diverse range of biological processes. For future therapeutic applications and for EV biology research in general, understanding the in vivo fate of EVs is of utmost importance. Here we studied biodistribution of EVs in mice after systemic delivery. EVs were isolated from 3 different mouse cell sources, including dendritic cells (DCs) derived from bone marrow, and labelled with a near-infrared lipophilic dye. Xenotransplantation of EVs was further carried out for cross-species comparison. The reliability of the labelling technique was confirmed by sucrose gradient fractionation, organ perfusion and further supported by immunohistochemical staining using CD63-EGFP probed vesicles. While vesicles accumulated mainly in liver, spleen, gastrointestinal tract and lungs, differences related to EV cell origin were detected. EVs accumulated in the tumour tissue of tumour-bearing mice and, after introduction of the rabies virus glycoprotein-targeting moiety, they were found more readily in acetylcholine-receptor-rich organs. In addition, the route of administration and the dose of injected EVs influenced the biodistribution pattern. This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b8a644883e1931598cf6f589210a7100540722c6

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Citations in the corpus

Using exosomes, naturally-equipped nanocarriers, for drug delivery (2015, background): “Several studies indicate that extracellular vesicles, such as exosomes, have a specific cell tropism, according to their characteristics and origin, which can be used to target them to disease tissues and/or organs [12].”
Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper (2015, methodology): “In addition to safety issues, the route of administration must be defined by answering the following questions: Are the EV fractions intended to be applied systemically or topically into affected tissues, and will they be administered once or repetitively? Does the route of injection affect the rela”
Advances in therapeutic applications of extracellular vesicles (2019, background): “Last, the route of administration of EVs influences their biodistribution (22), which needs to be considered when developing any therapeutic modality to be used in patients.”
Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment (2018, neutral): “We did incorporate a targeting moiety in our device, but although RVG-Lamp2b was reported to target exosomes to the brain 37 , we did not ﬁ nd that it increased the delivery of therapeutic exosomes to this organ at least in the present context.”
Development of Exosome-encapsulated Paclitaxel to Overcome MDR in Cancer cells (2015, neutral): “Several studies indicate that exosomes may have a specific cell tropism, according to their characteristics and origin, which can be used to target them to disease tissues and/or organs (26).”