Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting
Open accessAbstract
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.
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Intraperitoneal injections of fluorescent SkM-ELVs result in fluorescent labeling of 9 organs in mice.
“Intraperitoneal injections of fluorescent SkM-ELVs resulted in the fluorescent labeling of 9 organs in mice”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Wiklander et al., 2015
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Multifunctional role of exosomes in viral diseases: From transmission to diagnosis and therapy
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Stem cell secretome, regeneration, and clinical translation: a narrative review
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Engineered extracellular vesicles as brain therapeutics
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Exosome-like Nanoparticles: A New Type of Nanocarrier
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Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis
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MiR-128-3p – a gray eminence of the human central nervous system
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- Authors
- Wiklander, O. P. B., Nordin, J. Z., O'Loughlin, A., Gustafsson, Y., Corso, G., Mäger, I., Vader, P., Lee, Y., Sork, H., Seow, Y., Heldring, N., Alvarez‐Erviti, L., Smith, C. E., Le Blanc, K., Macchiarini, P., Jungebluth, P., Wood, M. J. A., & Andaloussi, S. E.
- Affiliations
- Karolinska Institutet (SE)
- Department of Physiology, Anatomy and Genetics University of Oxford Oxford United Kingdom
- University of Oxford (GB)
- Agency for Science, Technology and Research (SG)
- UCL Queen Square Institute of Neurology (GB)
- Department of Laboratory Medicine Karolinska Institutet Stockholm Sweden
- Heidelberg University (DE)
- Corresponding author
- Andaloussi, Samir EL
- ORCID
- Venue
- Journal of Extracellular Vesicles
- Publisher
- Wiley
- Published
- 2015-01
- Volume
- 4
- Issue
- 1
- Pages
- 26316-26316
- ISSN
- 2001-3078 (ISSN-L)
- PMC
- PMC4405624
- OpenAlex
- W2071625709
- Cited by
- 1,730
- References
- 56
- Citations by year
- 2026: 214 · 2025: 199 · 2024: 206 · 2023: 220 · 2022: 208 · 2021: 197 · 2020: 164 · 2019: 119 · 2018: 84 · 2017: 66 · 2016: 43 · 2015: 9 · 2013: 1
- FWCI
- 29.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Extracellular Vesicles (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Vetenskapsrådet (VR K2014-64X-20742-07-5)
- Cancerfonden
- Society for Economic Anthropology
- Karolinska Institutet
- Wellcome
- Agency for Science, Technology and Research
- VINNOVA (2010-00501)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- extracellular vesicles, tissue distribution, systemic drug delivery, dendritic cells, xenotransplantation, tumor targeting, rabies virus glycoprotein, acetylcholine receptor, route of administration, dose-dependent effects, liver and spleen accumulation
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