Cited by 385Extracellular vesicles in diseaseNanoparticle-Based Drug DeliveryRNA Interference and Gene Delivery

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 access

Watson, Dionysios C., Bayik, Defne, Srivatsan, Avinash, Bergamaschi, Cristina, Valentin, Antonio, Niu, Gang, Bear, Jenifer, Monninger, Mitchell, Sun, Mei, Morales-Kastresana, Aizea, Jones, Jennifer C., Felber, Barbara K., Chen, Xiaoyuan, Gursel, Ihsan, Pavlakis, George N.·2016·Biomaterials

DOI 10.1016/j.biomaterials.2016.07.003PMC PMC7156278

Open this paper in CoChat — free account Open PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.biomaterials.2016.07.003

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes
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
Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting
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
How pure are your vesicles?
Webber, J., & Clayton, A. (2013) · Journal of Extracellular Vesicles · doi:10.3402/jev.v2i0.19861 · Cited by 817
A Protocol for Exosome Isolation and Characterization: Evaluation of Ultracentrifugation, Density-Gradient Separation, and Immunoaffinity Capture Methods
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
Redistribution, Hyperproliferation, Activation of Natural Killer Cells and CD8 T Cells, and Cytokine Production During First-in-Human Clinical Trial of Recombinant Human Interleukin-15 in Patients With Cancer
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

Show all 40 references

Sorted by citations

Extracellular vesicles as drug delivery systems: Why and how?
Elsharkasy, O. M., Nordin, J. Z., Hagey, D. W., de Jong, O. G., Schiffelers, R. M., Andaloussi, S. E., & Vader, P. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.04.004 · Cited by 1,235
Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes
Gurunathan, S., Kang, M.-H., Jeyaraj, M., Qasim, M., & Kim, J. (2019) · Cells · doi:10.3390/cells8040307 · Cited by 1,160
Exosomes: Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake
Kimiz-Gebologlu, I., & Oncel, S. S. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.05.027 · Cited by 722
Extracellular vesicles in immunomodulation and tumor progression
Marar, C., Starich, B., & Wirtz, D. (2021) · Nature Immunology · doi:10.1038/s41590-021-00899-0 · Cited by 616
Review on Strategies and Technologies for Exosome Isolation and Purification
Chen, J., Li, P., Zhang, T., Xu, Z., Huang, X., Wang, R., & Du, L. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.811971 · Cited by 585
Efficient Angiogenesis-Based Diabetic Wound Healing/Skin Reconstruction through Bioactive Antibacterial Adhesive Ultraviolet Shielding Nanodressing with Exosome Release
Wang, M., Wang, C., Chen, M., Xi, Y., Cheng, W., Mao, C., Xu, T., Zhang, X., Lin, C., Gao, W., et al. (2019) · ACS Nano · doi:10.1021/acsnano.9b03656 · Cited by 556
Surface functionalization of exosomes for target-specific delivery and in vivo imaging & tracking: Strategies and significance
Salunkhe, S. A., Dheeraj, Basak, M., Chitkara, D., & Mittal, A. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.07.042 · Cited by 513
Native and bioengineered extracellular vesicles for cardiovascular therapeutics
de Abreu, R. C., Fernandes, H., Martins, P. A. D. C., Sahoo, S., Emanueli, C., & Ferreira, L. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0389-5 · Cited by 509
Extracellular vesicle-loaded hydrogels for tissue repair and regeneration
Ju, Y., Hu, Y., Pu, Y., Xie, X., & Fang, B. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100522 · Cited by 471
Extracellular vesicle isolation methods: rising impact of size-exclusion chromatography
Tortajada, M., Gálvez‐Montón, C., Bayés‐Genís, A., Roura, S., & Borràs, F. E. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03071-y · Cited by 469
Engineered Extracellular Vesicles for Cancer Therapy
Zhang, X., Zhang, H., Gu, J., Zhang, J., Shi, H., Qian, H., Wang, D., Xu, W., Pan, J., & Santos, H. A. (2021) · Advanced Materials · doi:10.1002/adma.202005709 · Cited by 428
Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation
Mol, E. A., Goumans, M., Doevendans, P. A., Sluijter, J. P. G., & Vader, P. (2017) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2017.03.011 · Cited by 426
Exosomes in Cancer Nanomedicine and Immunotherapy: Prospects and Challenges
Syn, N. L. X., Wang, L., Chow, E. K., Lim, C. T., & Goh, B.-C. (2017) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.03.004 · Cited by 405
Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration
Brennan, M. Á., Layrolle, P., & Mooney, D. J. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909125 · Cited by 399
Extracellular vesicles: A bright star of nanomedicine
Wu, P., Zhang, B., Ocansey, D. K. W., Xu, W., & Qian, H. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120467 · Cited by 368
Labeling Extracellular Vesicles for Nanoscale Flow Cytometry
Morales‐Kastresana, A., Telford, B., Musich, T., McKinnon, K. M., Clayborne, C., Braig, Z., Rosner, A., Demberg, T., Watson, D. C., Karpova, T., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01731-2 · Cited by 378
Self-citation
Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application
Yamashita, T., Takahashi, Y., & Takakura, Y. (2018) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b18-00133 · Cited by 309
Recent advances in exosome-mediated nucleic acid delivery for cancer therapy
Zhang, Y., Liu, Q., Zhang, X., Huang, H., Tang, S., Chai, Y., Xu, Z., Li, M., Chen, X., Liu, J., et al. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01472-z · Cited by 306
Self-citation
Advances in Exosome-Based Drug Delivery and Tumor Targeting: From Tissue Distribution to Intracellular Fate
Shao, J., Zaro, J., & Shen, Y. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s281890 · Cited by 295
Internalization of Exosomes through Receptor-Mediated Endocytosis
Gonda, A., Kabagwira, J., Senthil, G. N., & Wall, N. R. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0891 · Cited by 296
Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading
Rädler, J., Gupta, D., Zickler, A. M., & Andaloussi, S. E. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.02.013 · Cited by 298
Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics
Charoenviriyakul, C., Takahashi, Y., Morishita, M., Matsumoto, A., Nishikawa, M., & Takakura, Y. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.10.009 · Cited by 281
Biocompatibility of highly purified bovine milk‐derived extracellular vesicles
Somiya, M., Yoshioka, Y., & Ochiya, T. (2018) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2018.1440132 · Cited by 286
Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury
Cao, J., Wang, B., Tang, T., Lv, L., Ding, Z., Li, Z., Hu, R., Wei, Q., Shen, A., Fu, Y., et al. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01719-2 · Cited by 264
An improvised one-step sucrose cushion ultracentrifugation method for exosome isolation from culture supernatants of mesenchymal stem cells
Gupta, S., Rawat, S. J., Arora, V., Kottarath, S. K., Dinda, A. K., Vaishnav, P. K., Nayak, B., & Mohanty, S. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-0923-0 · Cited by 261
Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency
Willis, G. R., Kourembanas, S., & Mitsialis, S. A. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00063 · Cited by 267
Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell‐derived extracellular vesicles
Patel, D. B., Gray, K. M., Santharam, Y., Lamichhane, T. N., Stroka, K. M., & Jay, S. M. (2017) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10065 · Cited by 262
Immune Cell-Derived Extracellular Vesicles – Functions and Therapeutic Applications
Veerman, R. E., Akpinar, G. G., Eldh, M., & Gabrielsson, S. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.02.003 · Cited by 251
Exosomes Engineered to Express a Cardiomyocyte Binding Peptide Demonstrate Improved Cardiac Retention in Vivo
Mentkowski, K. I., & Lang, J. K. (2019) · Scientific Reports · doi:10.1038/s41598-019-46407-1 · Cited by 244
Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity
Yan, L., & Wu, X. (2019) · Cell Biology and Toxicology · doi:10.1007/s10565-019-09504-5 · Cited by 244
Pharmacokinetics of Exosomes—An Important Factor for Elucidating the Biological Roles of Exosomes and for the Development of Exosome-Based Therapeutics
Morishita, M., Takahashi, Y., Nishikawa, M., & Takakura, Y. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.02.030 · Cited by 233
Camouflage strategies for therapeutic exosomes evasion from phagocytosis
Parada, N., Romero-Trujillo, A., Georges, N., & Alcayaga‐Miranda, F. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.01.001 · Cited by 241
Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile
Zhang, L., He, F.-J., Gao, L., Cong, M., Sun, J., Xu, J., Wang, Y., Hu, Y., Asghar, S., Hu, L., et al. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s293067 · Cited by 234
Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells
Wang, J., Zheng, Y., & Zhao, M. L. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00533 · Cited by 229
Exosomes as a next-generation drug delivery system: An update on drug loading approaches, characterization, and clinical application challenges
Mehryab, F., Rabbani, S., Shahhosseini, S., Shekari, F., Fatahi, Y., Baharvand, H., & Haeri, A. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.06.036 · Cited by 216
Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging
Gupta, D., Liang, X., Pavlova, S., Wiklander, O. P. B., Corso, G., Zhao, Y. H., Saher, O., Bost, J., Zickler, A. M., Piffkó, A., et al. (2020) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2020.1800222 · Cited by 215
Extracellular vesicles as a drug delivery system: A systematic review of preclinical studies
de Castilla, P. E. M., Tong, L., Huang, C., Sofias, A. M., Pastorin, G., Chen, X. S., Storm, G., Schiffelers, R. M., & Wang, J. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.05.011 · Cited by 219
Self-citation
Extracellular Microvesicles as New Industrial Therapeutic Frontiers
Agrahari, V., Agrahari, V., Burnouf, P., Chew, C. H., & Burnouf, T. (2019) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.11.012 · Cited by 215
Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina
Driedonks, T. A. P., Jiang, L., Carlson, B., Han, Z., Liu, G., Queen, S. E., Shirk, E. N., Gololobova, O. A., Liao, Z., Nyberg, L. H., et al. (2022) · Journal of Extracellular Biology · doi:10.1002/jex2.59 · Cited by 209
Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation
Maumus, M., Rozier, P., Boulestreau, J., Jorgensen, C., & Noël, D. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00997 · Cited by 203
The potential and promise of IL-15 in immuno-oncogenic therapies
Robinson, T. O., & Schluns, K. S. (2017) · Immunology Letters · doi:10.1016/j.imlet.2017.08.010 · Cited by 191
Clinical Application of Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapeutics for Inflammatory Lung Diseases
Fujita, Y., Kadota, T., Araya, J., Ochiya, T., & Kuwano, K. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7100355 · Cited by 188
Scalable Production of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Under Serum-/Xeno-Free Conditions in a Microcarrier-Based Bioreactor Culture System
Fuzeta, M. D. A., Bernardes, N., Oliveira, F. D., Costa, A. C., Fernandes‐Platzgummer, A., Farinha, J. P. S., Rodrigues, C. A. V., Jung, S., Tseng, R.-J., Milligan, W. D., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.553444 · Cited by 194
Scalable, cGMP‐compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL‐15/lactadherin complexes
Watson, D. C., Yung, B. C., Bergamaschi, C., Chowdhury, B., Bear, J., Stellas, D., Morales‐Kastresana, A., Jones, J. C., Felber, B. K., Chen, X. S., et al. (2018) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2018.1442088 · Cited by 182
Self-citation
Technological advances towards extracellular vesicles mass production
Grangier, A., Branchu, J., Volatron, J., Piffoux, M., Gazeau, F., Wilhelm, C., & Silva, A. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113843 · Cited by 183
Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering
Liang, Y., Iqbal, Z., Lu, J., Wang, J., Zhang, H., Chen, X., Duan, L., & Xia, J. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2022.10.008 · Cited by 162
Self-citation
Tetraspanins are unevenly distributed across single extracellular vesicles and bias sensitivity to multiplexed cancer biomarkers
Mizenko, R. R., Brostoff, T., Rojalin, T., Koster, H. J., Swindell, H. S., Leiserowitz, G. S., Wang, A., & Carney, R. P. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00987-1 · Cited by 161
Scalable Production and Isolation of Extracellular Vesicles: Available Sources and Lessons from Current Industrial Bioprocesses
Paganini, C., Palmiero, U. C., Pòcsfalvi, G., Touzet, N., Bongiovanni, A., & Arosio, P. (2019) · Biotechnology Journal · doi:10.1002/biot.201800528 · Cited by 162
Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review
Ng, C. Y., Kee, L. T., Al-Masawa, M. E., Lee, Q. H., Subramaniam, T., Kok, D., Ng, M. H., & Law, J. X. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147986 · Cited by 157
Methods of the Large-Scale Production of Extracellular Vesicles
Syromiatnikova, V., Prokopeva, A. E., & Gomzikova, M. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810522 · Cited by 164
Enhanced extracellular vesicle production and ethanol-mediated vascularization bioactivity via a 3D-printed scaffold-perfusion bioreactor system
Patel, D. B., Luthers, C. R., Lerman, M. J., Fisher, J. P., & Jay, S. M. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.11.024 · Cited by 152
Engineered extracellular vesicles with synthetic lipids via membrane fusion to establish efficient gene delivery
Jhan, Y., Prasca-Chamorro, D., Zuniga, G. P., Moore, D. M., Kumar, S. A., Gaharwar, A. K., & Bishop, C. J. (2019) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.118802 · Cited by 157
Stem Cell-Derived Exosomes: a New Strategy of Neurodegenerative Disease Treatment
Hosseini, N. F., Sheykhhasan, M., Asl, S. S., & Najafi, R. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02324-x · Cited by 155
Extracellular Vesicles as an Efficient and Versatile System for Drug Delivery
Dang, X. T. T., Jayasinghe, M. K., Zhang, D. X., Pirisinu, M., & Le, M. T. N. (2020) · Cells · doi:10.3390/cells9102191 · Cited by 154
Exosomes: Cell-Derived Nanoplatforms for the Delivery of Cancer Therapeutics
Kim, H., Kim, E. H., Kwak, G., Chi, S.-G., Kim, S. H., & Yang, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010014 · Cited by 149
An Update on in Vivo Imaging of Extracellular Vesicles as Drug Delivery Vehicles
Gangadaran, P., Hong, C. M., & Ahn, B. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00169 · Cited by 145
Membrane Radiolabelling of Exosomes for Comparative Biodistribution Analysis in Immunocompetent and Immunodeficient Mice - A Novel and Universal Approach
Faruqu, F. N., Wang, J. T.-W., Xu, L., McNickle, L., Chong, E. M.-Y., Walters, A. A., Gurney, M., Clayton, A., Smyth, L. A., Hider, R. C., et al. (2019) · Theranostics · doi:10.7150/thno.27891 · Cited by 146
Metabolic signature of extracellular vesicles depends on the cell culture conditions
Palviainen, M., Saari, H., Kärkkäinen, O. K., Pekkinen, J., Auriola, S. O. K., Yliperttula, M. L., Puhka, M., Hanhineva, K., & Siljander, P. R. M. (2019) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2019.1596669 · Cited by 144
Systematic review of targeted extracellular vesicles for drug delivery – Considerations on methodological and biological heterogeneity
Gudbergsson, J. M., Jønsson, K., Simonsen, J. B., & Johnsen, K. B. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.06.006 · Cited by 139
Extracellular vesicle-based Nanotherapeutics: Emerging frontiers in anti-inflammatory therapy
Tang, T., Wang, B., Lv, L., & Liu, B. (2020) · Theranostics · doi:10.7150/thno.47865 · Cited by 137
Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma
Rosenberger, L., Ezquer, M., Lillo-Vera, F., Pedraza, P. L., Ortúzar, M. I., González, P. L., Figueroa‐Valdés, A. I., Cuenca, J., Ezquer, F. E., Khoury, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-36855-6 · Cited by 138
Clinical applications for exosomes: Are we there yet?
Perocheau, D., Touramanidou, L., Gurung, S., Gissen, P., & Baruteau, J. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15432 · Cited by 123
Small extracellular vesicles in cancer
Abhange, K. K., Makler, A., Wen, Y., Ramnauth, N., Mao, W., Asghar, W., & Wan, Y. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.03.015 · Cited by 139
Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
Gobin, J., Muradia, G., Mehic, J., Westwood, C., Couvrette, L. J., Stalker, A., Bigelow, S., Luebbert, C., Bissonnette, F. S.-D., Johnston, M., et al. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02190-3 · Cited by 125
Extracellular vesicles for personalized medicine: The input of physically triggered production, loading and theranostic properties
Piffoux, M., Nicolás‐Boluda, A., Mulens-Arias, V., Richard, S., Rahmi, G., Gazeau, F., Wilhelm, C., & Silva, A. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.12.009 · Cited by 130
Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma
Monfared, H., Jahangard, Y., Nikkhah, M., Mirnajafi-Zadeh, J., & Mowla, S. J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00782 · Cited by 123
“(38) showed that yield of exosomes can be increased by 5–10 fold using a hollow fiber bioreactor.”
Method
Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration
Zhang, B., Tian, X., Hao, J., Xu, G., & Zhang, W. (2020) · Cell Transplantation · doi:10.1177/0963689720908500 · Cited by 124
Nanoparticle based medicines: approaches for evading and manipulating the mononuclear phagocyte system and potential for clinical translation
Mills, J. A., Liu, F., Jarrett, T. R., Fletcher, N. L., & Thurecht, K. J. (2022) · Biomaterials Science · doi:10.1039/d2bm00181k · Cited by 128
Extracellular vesicle therapeutics for liver disease
Borrelli, D. A., Yankson, K., Shukla, N., Vilanilam, G. K., Ticer, T. D., & Wolfram, J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.01.022 · Cited by 120
Extracellular Vesicles as an Emerging Treatment Option for Intervertebral Disc Degeneration: Therapeutic Potential, Translational Pathways, and Regulatory Considerations
DiStefano, T. J., Vaso, K., Danias, G., Chionuma, H. N., Weiser, J. R., & Iatridis, J. C. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202100596 · Cited by 115
Strategies for scalable manufacturing and translation of MSC-derived extracellular vesicles
Adlerz, K. M., Patel, D. B., Rowley, J. A., Ng, K. S., & Ahsan, T. (2020) · Stem Cell Research · doi:10.1016/j.scr.2020.101978 · Cited by 122
Exosome therapeutics for lung regenerative medicine
Popowski, K. D., Lutz, H., Hu, S., George, A., Dinh, P., & Cheng, K. (2020) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2020.1785161 · Cited by 118
Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment
Patel, D. B., Santoro, M., Born, L. J., Fisher, J. P., & Jay, S. M. (2018) · Biotechnology Advances · doi:10.1016/j.biotechadv.2018.09.001 · Cited by 113
Therapeutic nanoplatforms and delivery strategies for neurological disorders
Kang, Y. J., Cutler, E. G., & Cho, H. (2018) · Nano Convergence · doi:10.1186/s40580-018-0168-8 · Cited by 114
Extracellular vesicle–matrix interactions
Debnath, K., Heras, K. L., Rivera, A., Lenzini, S. B., & Shin, J. (2023) · Nature Reviews Materials · doi:10.1038/s41578-023-00551-3 · Cited by 115
Strategies to overcome the main challenges of the use of exosomes as drug carrier for cancer therapy
Hussen, B. M., Faraj, G. S. H., Rasul, M. F., Hidayat, H. J., Salihi, A. B., Baniahmad, A., Taheri, M. N., & Ghafouri‐Fard, S. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02743-3 · Cited by 113
Strategies for the use of Extracellular Vesicles for the Delivery of Therapeutics
Sil, S., Dagur, R. S., Liao, K., Peeples, E. S., Hu, G., Periyasamy, P., & Buch, S. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09873-y · Cited by 109
Efficacy and safety of small extracellular vesicle interventions in wound healing and skin regeneration: A systematic review and meta-analysis of animal studies
Al-Masawa, M. E., Alshawsh, M. A., Ng, C. Y., Ng, M. H., Foo, J. B., Vijakumaran, U., Subramaniam, R., Ghani, N. A. A., Witwer, K. W., & Law, J. X. (2022) · Theranostics · doi:10.7150/thno.73436 · Cited by 115
Novel alternatives to extracellular vesicle-based immunotherapy – exosome mimetics derived from natural killer cells
Zhu, L., Gangadaran, P., Kalimuthu, S., Oh, J. M., Baek, S. H., Jeong, S. Y., Lee, S., Lee, J., & Ahn, B. (2018) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2018.1489824 · Cited by 107
Therapeutic Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Female Reproductive Diseases
Liao, Z., Liu, C., Wang, L., Sui, C., & Zhang, H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.665645 · Cited by 107
Accelerating Biologics Manufacturing by Modeling or: Is Approval under the QbD and PAT Approaches Demanded by Authorities Acceptable Without a Digital-Twin?
Zobel‐Roos, S., Schmidt, A., Mestmäcker, F., Mouellef, M., Huter, M., Uhlenbrock, L., Kornecki, M., Lohmann, L., Ditz, R., & Strube, J. (2019) · Processes · doi:10.3390/pr7020094 · Cited by 87
Engineered Extracellular Vesicles: Tailored-Made Nanomaterials for Medical Applications
Man, K., Brunet, M. Y., Jones, M., & Cox, S. C. (2020) · Nanomaterials · doi:10.3390/nano10091838 · Cited by 106
In vivo Non-invasive Imaging of Radio-Labeled Exosome-Mimetics Derived From Red Blood Cells in Mice
Gangadaran, P., Hong, C. M., Oh, J. M., Rajendran, R. L., Kalimuthu, S., Son, S. H., Gopal, A., Zhu, L., Baek, S. H., Jeong, S. Y., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00817 · Cited by 101
Bioglass enhances the production of exosomes and improves their capability of promoting vascularization
Wu, Z., He, D. N., & Li, H. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.09.011 · Cited by 103
Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease
Yin, T., Liu, Y., Ji, W., Zhuang, J., Chen, X., Gong, B., Chu, J., Liang, W., Gao, J., & Yin, Y. (2023) · Theranostics · doi:10.7150/thno.81860 · Cited by 107
Self-citation
Ageing and mesenchymal stem cells derived exosomes: Molecular insight and challenges
Ahmadi, M., & Rezaie, J. (2020) · Cell Biochemistry and Function · doi:10.1002/cbf.3602 · Cited by 103
Extracellular vesicles as an emerging drug delivery system for cancer treatment: Current strategies and recent advances
Wang, Z., Mo, H., He, Z., Chen, A., & Cheng, P. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113480 · Cited by 100
Extracellular vesicle-based therapeutics for the regeneration of chronic wounds: current knowledge and future perspectives
Lou, P., Liu, S., Xu, X., Pan, C., Lu, Y., & Liu, J. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.11.001 · Cited by 98
Natural Killer Cell-Derived Extracellular Vesicles: Novel Players in Cancer Immunotherapy
Wu, F., Xie, M., Hun, M., She, Z., Li, C., Luo, S., Chen, X., Wan, W., Wen, C., & Tian, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.658698 · Cited by 96
Self-citation
Exosome-Based Carrier for RNA Delivery: Progress and Challenges
Lu, Y., Huang, W. C., Li, M., & Zheng, A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020598 · Cited by 103
Extracellular‐Vesicle Isolation from Different Biological Fluids by Size‐Exclusion Chromatography
Tortajada, M., Font‐Morón, M., Gámez‐Valero, A., Carreras‐Planella, L., Borràs, F. E., & Franquesa, M. (2019) · Current Protocols in Stem Cell Biology · doi:10.1002/cpsc.82 · Cited by 93
Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine
Yin, L., Liu, X., Shi, Y., Ocansey, D. K. W., Hu, Y., Li, X., Zhang, C., Xu, W., & Qian, H. (2020) · Cells · doi:10.3390/cells9030707 · Cited by 92
Extracellular vesicles engineered to bind albumin demonstrate extended circulation time and lymph node accumulation in mouse models
Liang, X., Niu, Z., Galli, V., Howe, N., Zhao, Y. H., Wiklander, O. P. B., Zheng, W., Wiklander, R. J., Corso, G., Davies, C., et al. (2022) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12248 · Cited by 91
Strategies for persistent retention of macromolecules and nanoparticles in the blood circulation
Takakura, Y., & Takahashi, Y. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.05.063 · Cited by 91
Engineered Exosomes for Tumor-Targeted Drug Delivery: A Focus on Genetic and Chemical Functionalization
Akbari, A., Nazari‐Khanamiri, F., Ahmadi, M., Shoaran, M., & Rezaie, J. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics15010066 · Cited by 98
Differential in vivo biodistribution of 131I-labeled exosomes from diverse cellular origins and its implication for theranostic application
Rashid, M. H., Borin, T. F., Ara, R., Angara, K., Cai, J., Achyut, B. R., Liu, Y., & Arbab, A. S. (2019) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2019.102072 · Cited by 88
Angiogenic Effects of Human Dental Pulp and Bone Marrow-Derived Mesenchymal Stromal Cells and their Extracellular Vesicles
Merckx, G., Hosseinkhani, B., Kuypers, S., Deville, S., Irobi, J., Nelissen, I., Michiels, L., Lambrichts, I., & Bronckaers, A. (2020) · Cells · doi:10.3390/cells9020312 · Cited by 88
RETRACTED: Targeting and Therapy of Glioblastoma in a Mouse Model Using Exosomes Derived From Natural Killer Cells
Zhu, L., Oh, J. M., Gangadaran, P., Kalimuthu, S., Baek, S. H., Jeong, S. Y., Lee, S., Lee, J., & Ahn, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00824 · Cited by 86
Retracted
Targeted delivery of extracellular vesicles: the mechanisms, techniques and therapeutic applications
Zhao, S., Di, Y., Fan, H., Xu, C., Li, H., Wang, Y., Wang, W., Li, C., & Wang, J. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00230-x · Cited by 95
Therapeutic application of extracellular vesicles in kidney disease: promises and challenges
Lv, L., Wu, W., Ye, F., Li, Z., Tang, T., & Liu, B. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13407 · Cited by 84

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: Watson, Dionysios C.
Bergamaschi, Cristina
Valentin, Antonio
Niu, Gang
Bear, Jenifer
Jones, Jennifer C.
Felber, Barbara K.
Chen, Xiaoyuan
Pavlakis, George N.
Venue: Biomaterials
Publisher: Elsevier BV
Published: 2016-10
Volume: 105
Pages: 195-205
ISSN: 0142-9612 (ISSN-L)
DOI: 10.1016/j.biomaterials.2016.07.003
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Efficient production and enhanced tumor delivery of engineered extracellular vesicles

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks