The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Efficient production and enhanced tumor delivery of engineered extracellular vesicles
Open accessAbstract
Extracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles. We have used a hollow-fiber bioreactor for the efficient production of bioactive EV bearing the heterodimeric cytokine complex Interleukin-15:Interleukin-15 receptor alpha. Bioreactor culture yielded ∼40-fold more EV per mL conditioned medium, as compared to conventional cell culture. Biophysical analysis and comparative proteomics suggested a more diverse population of EV in the bioreactor preparations, while serum protein contaminants were detectable only in conventional culture EV preparations. We also identified the Scavenger Receptor Class A family (SR-A) as a novel monocyte/macrophage uptake receptor for EV. In vivo blockade of SR-A with dextran sulfate dramatically decreased EV liver clearance in mice, while enhancing tumor accumulation. These findings facilitate development of EV therapeutic methods.
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“Watson et al. (38) showed that yield of exosomes can be increased by 5–10 fold using a hollow fiber bioreactor.”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [38]
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Cites
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930
Zitvogel, L., Régnault, A., Lozier, A., Wolfers, J., Flament, C., Tenza, D., Ricciardi‐Castagnoli, P., Raposo, G., & Amigorena, S. (1998) · Nature Medicine · doi:10.1038/nm0598-594 · Cited by 2,266
Exosomes as drug delivery vehicles for Parkinson’s disease therapy
Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., Patel, T., Piroyan, A., Sokolsky, M., Kabanov, A. V., et al. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.03.033 · Cited by 2,009
Wiklander, O. P. B., Nordin, J. Z., O'Loughlin, A., Gustafsson, Y., Corso, G., Mäger, I., Vader, P., Lee, Y., Sork, H., Seow, Y., et al. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.26316 · Cited by 1,730
Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells
Ohno, S.-I., Takanashi, M., Sudo, K., Ueda, S., Ishikawa, A., Matsuyama, N., Fujita, K., Mizutani, T., Ohgi, T., Ochiya, T., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2012.180 · Cited by 1,666
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Greening, D. W., Xu, R., Ji, H. L., Tauro, B. J., & Simpson, R. J. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2550-6_15 · Cited by 749
Biodistribution and delivery efficiency of unmodified tumor-derived exosomes
Smyth, T., Kullberg, M., Malik, N., Smith-Jones, P. M., Graner, M. W., & Anchordoquy, T. J. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.12.013 · Cited by 738
Conlon, K. C., Lugli, E., Welles, H. C., Rosenberg, S. A., Fojo, A. T., Morris, J. C., Fleisher, T. A., Dubois, S. P., Perera, L. P., Stewart, D. M., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.57.3329 · Cited by 728
Production and characterization of clinical grade exosomes derived from dendritic cells
Lamparski, H., Mehta-Damani, A., Yao, J.-Y., Patel, S., Hsu, D., Ruegg, C. L., & Pecq, J. L. (2002) · Journal of Immunological Methods · doi:10.1016/s0022-1759(02)00330-7 · Cited by 701
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Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges
Ubanako, P., Mirza, S., Ruff, P., & Penny, C. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2024.1447953 · Cited by 68
Metadata
- Authors
- Watson, D. C., Bayik, D., Srivatsan, A., Bergamaschi, C., Valentin, A., Niu, G., Bear, J., Monninger, M., Sun, M., Morales-Kastresana, A., Jones, J. C., Felber, B. K., Chen, X., Gursel, I., & Pavlakis, G. N.
- Affiliations
- University of Patras (GR)
- National Institutes of Health (US)
- National Cancer Institute (US)
- Frederick National Laboratory for Cancer Research (US)
- United States Army Medical Research Institute of Infectious Diseases (US)
- Corresponding author
- Pavlakis, George N.
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 105
- Pages
- 195-205
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC7156278
- OpenAlex
- W2466551530
- Cited by
- 385
- References
- 40
- Citations by year
- 2026: 25 · 2025: 45 · 2024: 44 · 2023: 41 · 2022: 62 · 2021: 45 · 2020: 55 · 2019: 30 · 2018: 22 · 2017: 15 · 2016: 1
- FWCI
- 11.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biomaterials (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Bilkent University Institutional Repository (Bilkent University) (submittedVersion)
- Funders
- Intramural Research Program of the National Institutes of Health
- National Cancer Institute
- 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 › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- extracellular vesicles, exosomes, hollow fiber bioreactor, IL-15, IL-15Rα, cytokine delivery, tumor accumulation, hepatic clearance, scavenger receptor A, dextran sulfate, EV proteomics
- MeSH terms
- Extracellular Vesicles, Cell Fractionation, Cells, Cultured, Equipment Design, Humans, Macrophages, Neoplasms, Experimental, Bioreactors, Tissue Engineering, HEK293 Cells, Batch Cell Culture Techniques
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