Extracellular vesicles from organoids and 3D culture systems.
3D in vitro culture
exosome
extracellular vesicles
microvesicles
nanomedicine
organoids
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
08
01
2020
revised:
17
08
2020
accepted:
09
10
2020
pubmed:
22
10
2020
medline:
18
1
2022
entrez:
21
10
2020
Statut:
ppublish
Résumé
When discovered, extracellular vesicles (EVs) such as exosomes were thought of as junk carriers and a means by which the cell disposed of its waste material. Over the years, the role of EVs in cell communication has become apparent with the discovery that the nano-scale vesicles also transport RNA, DNA, and other bioactive components to and from the cells. These findings were originally made in EVs from body fluids of organisms and from in vitro two-dimensional (2D) cell culture models. Recently, organoids and other 3D multicellular in vitro models are being used to study EVs in the context of both physiologic and pathological states. However, standard, reproducible methods are lacking for EV analysis using these models. As a step toward understanding the implications of these platforms, this review provides a comprehensive picture of the progress using 3D in vitro culture models for EV analysis. Translational efforts and regulatory considerations for EV therapeutics are also briefly overviewed to understand what is needed for scale-up and, ultimately, commercialization.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1029-1049Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Abels, E. R., & Breakefield, X. O. (2016). Introduction to extracellular vesicles: Biogenesis, RNA cargo selection, content, release, and uptake. Cellular and Molecular Neurobiology, 36(3), 301-312. https://doi.org/10.1007/s10571-016-0366-z
Alibhai, F. J., Tobin, S. W., Yeganeh, A., Weisel, R. D., & Li, R.-K. (2018). Emerging roles of extracellular vesicles in cardiac repair and rejuvenation. American Journal of Physiology-Heart and Circulatory Physiology, 315(4), H733-H744. https://doi.org/10.1152/ajpheart.00100.2018
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature Biotechnology, 29(4), 341-345. https://doi.org/10.1038/nbt.1807
Antimisiaris, S. G., Mourtas, S., & Marazioti, A. (2018). Exosomes and exosome-inspired vesicles for targeted drug delivery. Pharmaceutics, 10(4), 218. https://doi.org/10.3390/pharmaceutics10040218
Balachandran, B., & Yuana, Y. (2019). Extracellular vesicles-based drug delivery system for cancer treatment. Cogent Medicine, 6(1), 1635806. https://doi.org/10.1080/2331205X.2019.1635806
Bauman, E., Feijão, T., Carvalho, D. T. O., Granja, P. L., & Barrias, C. C. (2018). Xeno-free pre-vascularized spheroids for therapeutic applications. Scientific Reports, 8(1), 230. https://doi.org/10.1038/s41598-017-18431-6
Besse, B., Charrier, M., Lapierre, V., Dansin, E., Lantz, O., Planchard, D., Le Chevalier, T., Livartoski, A., Barlesi, F., Laplanche, A., Ploix, S., Vimond, N., Peguillet, I., Théry, C., Lacroix, L., Zoernig, I., Dhodapkar, K., Dhodapkar, M., Viaud, S., … Chaput, N. (2015). Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology, 5(4), e1071008. https://doi.org/10.1080/2162402X.2015.1071008
Bhattacharya, S., Calar, K., Evans, C., Petrasko, M., & de la Puente, P. (2019). Bioengineering a novel 3D in-vitro model to recreate physiological oxygen levels and tumor-immune interactions. bioRxiv, 828145. https://doi.org/10.1101/828145
Bollini, S., Smits, A. M., Balbi, C., Lazzarini, E., & Ameri, P. (2018). Triggering endogenous cardiac repair and regeneration via extracellular vesicle-mediated communication. Frontiers in Physiology, 9, 1497-1497. https://doi.org/10.3389/fphys.2018.01497
Borosch, S., Dahmen, E., Beckers, C., Stoppe, C., Buhl, E. M., Denecke, B., Goetzenich, A., & Kraemer, S. (2017). Characterization of extracellular vesicles derived from cardiac cells in an in vitro model of preconditioning. Journal of Extracellular Vesicles, 6(1), 1390391. https://doi.org/10.1080/20013078.2017.1390391
Chen, I.-H., Xue, L., Hsu, C.-C., Paez, J. S. P., Pan, L., Andaluz, H., Wendt, M. K., Iliuk, A. B., Zhu, J. K., & Tao, W. A. (2017). Phosphoproteins in extracellular vesicles as candidate markers for breast cancer. Proceedings of the National Academy of Sciences, 114(12), 3175-3180. https://doi.org/10.1073/pnas.1618088114
Chiang, C.-y, & Chen, C. (2019). Toward characterizing extracellular vesicles at a single-particle level. Journal of Biomedical Science, 26(1), 9. https://doi.org/10.1186/s12929-019-0502-4
Clevers, H. (2016). Modeling development and disease with organoids. Cell, 165(7), 1586-1597. https://doi.org/10.1016/j.cell.2016.05.082
Crawford, S., Diamond, D., Brustolon, L., & Penarreta, R. (2010). Effect of increased extracellular Ca2+ on microvesicle production and tumor spheroid formation. Cancer Microenvironment, 4(1), 93-103. https://doi.org/10.1007/s12307-010-0049-0
Crewe, C., Joffin, N., Rutkowski, J. M., Kim, M., Zhang, F., Towler, D. A., Gordillo, R., & Scherer, P. E. (2018). An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state. Cell, 175(3), 695-708.e613. https://doi.org/10.1016/j.cell.2018.09.005
Dai, S., Wei, D., Wu, Z., Zhou, X., Wei, X., Huang, H., & Li, G. (2008). Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Molecular Therapy, 16(4), 782-790. https://doi.org/10.1038/mt.2008.1
Dar, A., Gerecht, S., & Itskovitz-Eldor, J. (2013). Human vascular progenitor cells. In R. Lanza, & A. Atala (Eds.), Handbook of stem cells (2nd ed., pp. 587-594). Academic Press.
Deatherage, B. L., & Cookson, B. T. (2012). Membrane vesicle release in bacteria, eukaryotes, and archaea: A conserved yet underappreciated aspect of microbial life. Infection and Immunity, 80(6), 1948-1957. https://doi.org/10.1128/IAI.06014-11
de Abreu, R. C., Fernandes, H., da Costa Martins, P. A., Sahoo, S., Emanueli, C., & Ferreira, L. (2020). Native and bioengineered extracellular vesicles for cardiovascular therapeutics. Nature Reviews Cardiology, 17, 685-697. https://doi.org/10.1038/s41569-020-0389-5
Dekkers, J. F., Wiegerinck, C. L., de Jonge, H. R., Bronsveld, I., Janssens, H. M., de Winter-de Groot, K. M., Brandsma, A. M., de Jong, N. W. M., Bijvelds, M. J. C., Scholte, B. J., Nieuwenhuis, E. E. S., van den Brink, S., Clevers, H., van der Ent, C. K., Middendorp, S., & Beekman, J. M. (2013). A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nature Medicine, 19, 939-945.
Di Lullo, E., & Kriegstein, A. R. (2017). The use of brain organoids to investigate neural development and disease. Nature Reviews Neuroscience, 18, 573-584. https://doi.org/10.1038/nrn.2017.107
Dias, M. V. S., Costa, C. S., & daSilva, L. L. P. (2018). The ambiguous roles of extracellular vesicles in HIV replication and pathogenesis. Frontiers in Microbiology, 9, 2411-2411. https://doi.org/10.3389/fmicb.2018.02411
Diomede, F., Gugliandolo, A., Cardelli, P., Merciaro, I., Ettorre, V., Traini, T., Bedini, R., Scionti, D., Bramanti, A., Nanci, A., Caputi, S., Fontana, A., Mazzon, E., & Trubiani, O. (2018). Three-dimensional printed PLA scaffold and human gingival stem cell-derived extracellular vesicles: A new tool for bone defect repair. Stem Cell Research & Therapy, 9(1), 104. https://doi.org/10.1186/s13287-018-0850-0
Dreyer, F., & Baur, A. (2016). Biogenesis and functions of exosomes and extracellular vesicles. In M. Federico (Ed.), Lentiviral vectors and exosomes as gene and protein delivery tools (pp. 201-216). Springer.
Drost, J., & Clevers, H. (2018). Organoids in cancer research. Nature Reviews Cancer, 18(7), 407-418. https://doi.org/10.1038/s41568-018-0007-6
Duval, K., Grover, H., Han, L.-H., Mou, Y., Pegoraro, A. F., Fredberg, J., & Chen, Z. (2017). Modeling physiological events in 2D vs. 3D cell culture. Physiology, 32(4), 266-277. https://doi.org/10.1152/physiol.00036.2016
Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014). Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay and Drug Development Technologies, 12(4), 207-218. https://doi.org/10.1089/adt.2014.573
Eiraku, M., Watanabe, K., Matsuo-Takasaki, M., Kawada, M., Yonemura, S., Matsumura, M., Wataya, T., Nishiyama, A., Muguruma, K., & Sasai, Y. (2008). Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell, 3(5), 519-532. https://doi.org/10.1016/j.stem.2008.09.002
El Andaloussi, S., Mäger, I., Breakefield, X. O., & Wood, M. J. A. (2013). Extracellular vesicles: Biology and emerging therapeutic opportunities. Nature Reviews Drug Discovery, 12, 347-357. https://doi.org/10.1038/nrd3978
Escudier, B., Dorval, T., Chaput, N., André, F., Caby, M.-P., Novault, S., Flament, C., Leboulaire, C., Borg, C., Amigorena, S., Boccaccio, C., Bonnerot, C., Dhellin, O., Movassagh, M., Piperno, S., Robert, C., Serra, V., Valente, N., Le Pecq, J. B., … Zitvogel, L. (2005). Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: Results of thefirst phase I clinical trial. Journal of Translational Medicine, 3(1), 10-10. https://doi.org/10.1186/1479-5876-3-10
Fang, Y., & Eglen, R. M. (2017). Three-dimensional cell cultures in drug discovery and development. SLAS Discovery, 22(5), 456-472. https://doi.org/10.1177/1087057117696795
Fatehullah, A., Tan, S. H., & Barker, N. (2016). Organoids as an in vitro model of human development and disease. Nature Cell Biology, 18, 246-254. https://doi.org/10.1038/ncb3312
Foty, R. (2011). A simple hanging drop cell culture protocol for generation of 3D spheroids. Journal of Visualized Experiments, 51), 2720. https://doi.org/10.3791/2720
Fukuda, M., Mizutani, T., Mochizuki, W., Matsumoto, T., Nozaki, K., Sakamaki, Y., Ichinose, S., Okada, Y., Tanaka, T., Watanabe, M., & Nakamura, T. (2014). Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. Genes & Development, 28(16), 1752-1757. https://doi.org/10.1101/gad.245233.114
Fuster-Matanzo, A., Gessler, F., Leonardi, T., Iraci, N., & Pluchino, S. (2015). Acellular approaches for regenerative medicine: On the verge of clinical trials with extracellular membrane vesicles? Stem Cell Research & Therapy, 6(1), 227. https://doi.org/10.1186/s13287-015-0232-9
Gao, L., Gregorich, Z. R., Zhu, W., Mattapally, S., Oduk, Y., Lou, X., Kannappan, R., Borovjagin, A. V., Walcott, G. P., Pollard, A. E., Fast, V. G., Hu, X., Lloyd, S. G., Ge, Y., & Zhang, J. (2018). Large cardiac muscle patches engineered from human induced-pluripotent stem cell-derived cardiac cells improve recovery from myocardial infarction in swine. Circulation, 137(16), 1712-1730. https://doi.org/10.1161/CIRCULATIONAHA.117.030785
Gerecht-Nir, S., & Itskovitz-Eldor, J. (2004). Vascular progenitor cells in the human model. In R. Lanza, J. Gearhart, B. Hogan, D. Melton, R. Pedersen, J. Thomson, & M. West (Eds.), Handbook of stem cells (pp. 323-328). Academic Press.
Grassi, L., Alfonsi, R., Francescangeli, F., Signore, M., De Angelis, M. L., Addario, A., Costantini, M., Flex, E., Ciolfi, A., Pizzi, S., Bruselles, A., Pallocca, M., Simone, G., Haoui, M., Falchi, M., Milella, M., Sentinelli, S., Di Matteo, P., Stellacci, E., … Bonci, D. (2019). Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases. Cell Death & Disease, 10(3), 201. https://doi.org/10.1038/s41419-019-1453-0
Greening, D. W., Xu, R., Ji, H., Tauro, B. J., & Simpson, R. J. (2015). A protocol for exosome isolation and characterization: Evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods. In A. Posch (Ed.), Proteomic profiling: Methods and protocols (pp. 179-209). Springer.
Greggio, C., De Franceschi, F., Figueiredo-Larsen, M., Gobaa, S., Ranga, A., Semb, H., Lutolf, M., & Grapin-Botton, A. (2013). Artificial three-dimensional niches deconstruct pancreas development in vitro. Development, 140(21), 4452-4462. https://doi.org/10.1242/dev.096628
Gézsi, A., Kovács, Á., Visnovitz, T., & Buzás, E. I. (2019). Systems biology approaches to investigating the roles of extracellular vesicles in human diseases. Experimental & Molecular Medicine, 51(3), 33-11. https://doi.org/10.1038/s12276-019-0226-2
Haraszti, R. A., Miller, R., Stoppato, M., Sere, Y. Y., Coles, A., Didiot, M.-C., Wollacott, R., Sapp, E., Dubuke, M. L., Li, X., Shaffer, S. A., DiFiglia, M., Wang, Y., Aronin, N., & Khvorova, A. (2018). Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Molecular Therapy, 26(12), 2838-2847. https://doi.org/10.1016/j.ymthe.2018.09.015
Hartjes, T. A., Mytnyk, S., Jenster, G. W., van Steijn, V., & van Royen, M. E. (2019). Extracellular vesicle quantification and characterization: Common methods and emerging approaches. Bioengineering, 6(1), 7. https://doi.org/10.3390/bioengineering6010007
Ibrahim, A.hmedG.-E., Cheng, K., & Marbán, E. (2014). Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports, 2(5), 606-619. https://doi.org/10.1016/j.stemcr.2014.04.006
Infanger, D. W., Cho, Y., Lopez, B. S., Mohanan, S., Liu, S. C., Gursel, D., Boockvar, J. A., & Fischbach, C. (2013). Glioblastoma stem cells are regulated by interleukin-8 signaling in a tumoral perivascular niche. Cancer Research, 73(23), 7079-7089. https://doi.org/10.1158/0008-5472.can-13-1355
Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367(6478), eaau6977. https://doi.org/10.1126/science.aau6977
Kostarelos, K., Emfietzoglou, D., Papakostas, A., Yang, W.-H., Ballangrud, Å., & Sgouros, G. (2004). Binding and interstitial penetration of liposomes within avascular tumor spheroids. International Journal of Cancer, 112(4), 713-721. https://doi.org/10.1002/ijc.20457
Kowal, J., Arras, G., Colombo, M., Jouve, M., Morath, J. P., Primdal-Bengtson, B., Dingli, F., Loew, D., Tkach, M., & Théry, C. (2016). Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proceedings of the National Academy of Sciences, 113(8), E968-E977. https://doi.org/10.1073/pnas.1521230113
Kreimer, S., Belov, A. M., Ghiran, I., Murthy, S. K., Frank, D. A., & Ivanov, A. R. (2015). Mass-spectrometry-based molecular characterization of extracellular vesicles: Lipidomics and proteomics. Journal of Proteome Research, 14(6), 2367-2384. https://doi.org/10.1021/pr501279t
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013). Cerebral organoids model human brain development and microcephaly. Nature, 501, 373-379.
Lee, J., Kim, J., Jeong, M., Lee, H., Goh, U., Kim, H., Kim, B., & Park, J.-H. (2015). Liposome-based engineering of cells to package hydrophobic compounds in membrane vesicles for tumor penetration. Nano Letters, 15(5), 2938-2944. https://doi.org/10.1021/nl5047494
Lener, T., Gimona, M., Aigner, L., Börger, V., Buzas, E., Camussi, G., Chaput, N., Chatterjee, D., Court, F. A., Portillo, H. A., O'Driscoll, L., Fais, S., Falcon-Perez, J. M., Felderhoff-Mueser, U., Fraile, L., Gho, Y. S., Görgens, A., Gupta, R. C., Hendrix, A., … Giebel, B. (2015). Applying extracellular vesicles based therapeutics in clinical trials-An ISEV position paper. Journal of Extracellular Vesicles, 4(1), 30087. https://doi.org/10.3402/jev.v4.30087
Lichtenbeld, H. H., Muller, A. D., van Dam-Mieras, M. C., & Blijham, G. H. (1993). Tumor spheroid-induced vesicle formation on endothelial cells is associated with procoagulant properties. Journal of Cell Science, 106(2), 657.
Liu, B., Lee, B. W., Nakanishi, K., Villasante, A., Williamson, R., Metz, J., Kim, J., Kanai, M., Bi, L., Brown, K., Di Paolo, G., Homma, S., Sims, P. A., Topkara, V. K., & Vunjak-Novakovic, G. (2018). Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells. Nature Biomedical Engineering, 2(5), 293-303. https://doi.org/10.1038/s41551-018-0229-7
Liu, S., Mahairaki, V., Bai, H., Ding, Z., Li, J., Witwer, K. W., & Cheng, L. (2019). Highly purified human extracellular vesicles produced by stem cells alleviate aging cellular phenotypes of senescent human cells. Stem Cells, 37(6), 779-790. https://doi.org/10.1002/stem.2996
Maciel, E., & Mansuy, I. M. (2019). Extracellular vesicles and their miRNA Cargo: A means of communication between soma and germline in the mammalian reproductive system. CHIMIA International Journal for Chemistry, 73(5), 356-361. https://doi.org/10.2533/chimia.2019.356
Mahe, M. M., Sundaram, N., Watson, C. L., Shroyer, N. F., & Helmrath, M. A. (2015). Establishment of human epithelial enteroids and colonoids from whole tissue and biopsy. Journal of Visualized Experiments, 97), 52483. https://doi.org/10.3791/52483
Meckes, D. G., & Raab-Traub, N. (2011). Microvesicles and viral infection. Journal of Virology, 85(24), 12844-12854. https://doi.org/10.1128/jvi.05853-11
Mehta, G., Hsiao, A. Y., Ingram, M., Luker, G. D., & Takayama, S. (2012). Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. Journal of Controlled Release, 164(2), 192-204. https://doi.org/10.1016/j.jconrel.2012.04.045
Middleton, R. C., Rogers, R. G., De Couto, G., Tseliou, E., Luther, K., Holewinski, R., Soetkamp, D., Van Eyk, J. E., Antes, T. J., & Marbán, E. (2018). Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes. Journal of Extracellular Vesicles, 7(1), 1456888. https://doi.org/10.1080/20013078.2018.1456888
Millipore Sigma. (2019). 3D Organoid culture: New in vitro models of development and disease. Retrieved from www.sigmaaldrich.com/technical-documents/articles/biology/cell-culture/3d-organoid-culture.html#ref
Morad, G., Carman, C. V., Hagedorn, E. J., Perlin, J. R., Zon, L. I., Mustafaoglu, N., Park, T.-E., Ingber, D. E., Daisy, C. C., & Moses, M. A. (2019). Tumor-derived extracellular vesicles breach the intact blood-brain barrier via transcytosis. ACS Nano, 13, 13853-13865. https://doi.org/10.1021/acsnano.9b04397
Morse, M. A., Garst, J., Osada, T., Khan, S., Hobeika, A., Clay, T. M., Valente, N., Shreeniwas, R., Sutton, M., Delcayre, A., Hsu, D. H., Le Pecq, J. B., & Lyerly, H. K. (2005). A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. Journal of Translational Medicine, 3(1), 9. 9 https://doi.org/10.1186/1479-5876-3-9
Muratori, C., Cavallin, L. E., Krätzel, K., Tinari, A., De Milito, A., Fais, S., D'Aloja, P., Federico, M., Vullo, V., Fomina, A., Mesri, E. A., Superti, F., & Baur, A. S. (2009). Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef transfer to bystander cells. Cell Host & Microbe, 6(3), 218-230. https://doi.org/10.1016/j.chom.2009.06.009
Narayanan, K., Kumar, S., Padmanabhan, P., Gulyas, B., Wan, A. C. A., & Rajendran, V. M. (2018). Lineage-specific exosomes could override extracellular matrix mediated human mesenchymal stem cell differentiation. Biomaterials, 182, 312-322. https://doi.org/10.1016/j.biomaterials.2018.08.027
Nassar, W., El-Ansary, M., Sabry, D., Mostafa, M. A., Fayad, T., Kotb, E., Temraz, M., Saad, A.-N., Essa, W., & Adel, H. (2016). Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomaterials Research, 20(1), 21. https://doi.org/10.1186/s40824-016-0068-0
Nielsen, T., Kristensen, A. F., Pedersen, S., Christiansen, G., & Kristensen, S. R. (2018). Investigation of procoagulant activity in extracellular vesicles isolated by differential ultracentrifugation. Journal of Extracellular Vesicles, 7(1), 1454777. https://doi.org/10.1080/20013078.2018.1454777
Nolte-‘t Hoen, E., Cremer, T., Gallo, R. C., & Margolis, L. B. (2016). Extracellular vesicles and viruses: Are they close relatives? Proceedings of the National Academy of Sciences, 113(33), 9155-9161. https://doi.org/10.1073/pnas.1605146113
Ootani, A., Li, X., Sangiorgi, E., Ho, Q. T., Ueno, H., Toda, S., Sugihara, H., Fujimoto, K., Weissman, I. L., Capecchi, M. R., & Kuo, C. J. (2009). Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nature Medicine, 15, 701-706.
Patel, D. B., Gray, K. M., Santharam, Y., Lamichhane, T. N., Stroka, K. M., & Jay, S. M. (2017). Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles. Bioengineering & Translational Medicine, 2(2), 170-179. https://doi.org/10.1002/btm2.10065
Pașca, S. P. (2018). The rise of three-dimensional human brain cultures. Nature, 553, 437-445. https://doi.org/10.1038/nature25032
Popova, A. A., Tronser, T., Demir, K., Haitz, P., Kuodyte, K., Starkuviene, V., Wajda, P., & Levkin, P. A. (2019). Facile one step formation and screening of tumor spheroids using droplet-microarray platform. Small, 15(25), 1901299. https://doi.org/10.1002/smll.201901299
Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, G. R., Jacob, F., Zhong, C., Yoon, K., Jeang, W., Lin, L., Li, Y., Thakor, J., Berg, D. A., Zhang, C., Kang, E., Chickering, M., … Ming, G. (2016). Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell, 165(5), 1238-1254. https://doi.org/10.1016/j.cell.2016.04.032
Quadrato, G., Brown, J., & Arlotta, P. (2016). The promises and challenges of human brain organoids as models of neuropsychiatric disease. Nature Medicine, 22, 1220-1228. https://doi.org/10.1038/nm.4214
Rafatian, G., & Davis, D. R. (2018). Concise review: Heart-derived cell therapy 2.0: Paracrine strategies to increase therapeutic repair of injured myocardium. Stem Cells, 36(12), 1794-1803. https://doi.org/10.1002/stem.2910
Ratajczak, J., Miekus, K., Kucia, M., Zhang, J., Reca, R., Dvorak, P., & Ratajczak, M. Z. (2006). Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: Evidence for horizontal transfer of mRNA and protein delivery. Leukemia, 20(5), 847-856. https://doi.org/10.1038/sj.leu.2404132
Ravi, M., Paramesh, V., Kaviya, S. R., Anuradha, E., & Solomon, F. D. P. (2015). 3D cell culture systems: Advantages and applications. Journal of Cellular Physiology, 230(1), 16-26. https://doi.org/10.1002/jcp.24683
Reiner, A. T., Witwer, K. W., van Balkom, B. W. M., de Beer, J., Brodie, C., Corteling, R. L., Gabrielsson, S., Gimona, M., Ibrahim, A. G., de Kleijn, D., Lai, C. P., Lötvall, J., del Portillo, H. A., Reischl, I. G., Riazifar, M., Salomon, C., Tahara, H., Toh, W. S., Wauben, M. H. M., … Lim, S. K. (2017). Concise review: Developing best-practice models for the therapeutic use of extracellular vesicles. Stem Cells Translational Medicine, 6(8), 1730-1739. https://doi.org/10.1002/sctm.17-0055
Robbins, P. D., & Morelli, A. E. (2014). Regulation of immune responses by extracellular vesicles. Nature Reviews Immunology, 14, 195-208.
Rocha, S., Carvalho, J., Oliveira, P., Voglstaetter, M., Schvartz, D., Thomsen, A. R., Walter, N., Khanduri, R., Sanchez, J. C., Keller, A., Oliveira, C., & Nazarenko, I. (2019). 3D cellular architecture affects microRNA and protein cargo of extracellular vesicles. Advanced Science, 6(4), 1800948. https://doi.org/10.1002/advs.201800948
Rossi, G., Manfrin, A., & Lutolf, M. P. (2018). Progress and potential in organoid research. Nature Reviews Genetics, 19(11), 671-687. https://doi.org/10.1038/s41576-018-0051-9
Sadovska, L., Zandberga, E., Sagini, K., Jēkabsons, K., Riekstiņa, U., Kalniņa, Z., Llorente, A., & Linē, A. (2018). A novel 3D heterotypic spheroid model for studying extracellular vesicle-mediated tumour and immune cell communication. Biochemical and Biophysical Research Communications, 495(2), 1930-1935. https://doi.org/10.1016/j.bbrc.2017.12.072
Saha, P., Sharma, S., Korutla, L., Datla, S. R., Shoja-Taheri, F., Mishra, R., Bigham, G. E., Sarkar, M., Morales, D., Bittle, G., Gunasekaran, M., Ambastha, C., Arfat, M. Y., Li, D., Habertheuer, A., Hu, R., Platt, M. O., Yang, P., Davis, M. E., … Kaushal, S. (2019). Circulating exosomes derived from transplanted progenitor cells aid the functional recovery of ischemic myocardium. Science Translational Medicine, 11(493), eaau1168. https://doi.org/10.1126/scitranslmed.aau1168
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., & Clevers, H. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 459, 262-265.
Schneider, D. J., Speth, J. M., Penke, L. R., Wettlaufer, S. H., Swanson, J. A., & Peters-Golden, M. (2017). Mechanisms and modulation of microvesicle uptake in a model of alveolar cell communication. The Journal of Biological Chemistry, 292(51), 20897-20910. https://doi.org/10.1074/jbc.M117.792416
Sedgwick, A. E., & D'Souza-Schorey, C. (2018). The biology of extracellular microvesicles. Traffic, 19(5), 319-327. https://doi.org/10.1111/tra.12558
Shamir, E. R., & Ewald, A. J. (2014). Three-dimensional organotypic culture: Experimental models of mammalian biology and disease. Nature Reviews Molecular Cell Biology, 15, 647-664. https://doi.org/10.1038/nrm3873
Silva, A. M., Teixeira, J. H., Almeida, M. I., Gonçalves, R. M., Barbosa, M. A., & Santos, S. G. (2017). Extracellular vesicles: Immunomodulatory messengers in the context of tissue repair/regeneration. European Journal of Pharmaceutical Sciences, 98, 86-95. https://doi.org/10.1016/j.ejps.2016.09.017
Sittampalam, S., Eglen, R., Ferguson, S., Maynes, J. T., Olden, K., Schrader, L., Shelper, T., & Ferrer, M. (2015). Three-dimensional cell culture assays: Are they more predictive of in vivo efficacy than 2D monolayer cell-based assays? Assay and Drug Development Technologies, 13(5), 254-261. https://doi.org/10.1089/adt.2015.29001.rtd
Szvicsek, Z., Oszvald, Á., Szabó, L., Sándor, G. O., Kelemen, A., Soós, A. Á., Pálóczi, K., Harsányi, L., Tölgyes, T., Dede, K., Bursics, A., Buzás, E. I., Zeöld, A., & Wiener, Z. (2019). Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors. Cellular and Molecular Life Sciences, 76(12), 2463-2476. https://doi.org/10.1007/s00018-019-03052-1
Tabei, R., Kawaguchi, S., Kanazawa, H., Tohyama, S., Hirano, A., Handa, N., Hishikawa, S., Teratani, T., Kunita, S., Fukuda, J., Mugishima, Y., Suzuki, T., Nakajima, K., Seki, T., Kishino, Y., Okada, M., Yamazaki, M., Okamoto, K., Shimizu, H., … Fukuda, K. (2019). Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cell-derived cardiomyocytes. The Journal of Heart and Lung Transplantation, 38(2), 203-214. https://doi.org/10.1016/j.healun.2018.11.002
Takahashi, A., Okada, R., Nagao, K., Kawamata, Y., Hanyu, A., Yoshimoto, S., Takasugi, M., Watanabe, S., Kanemaki, M. T., Obuse, C., & Hara, E. (2017). Exosomes maintain cellular homeostasis by excreting harmful DNA from cells. Nature Communications, 8, 15287.
Takasato, M., Er, P. X., Chiu, H. S., Maier, B., Baillie, G. J., Ferguson, C., Parton, R. G., Wolvetang, E. J., Roost, M. S., Chuva de Sousa Lopes, S. M., & Little, M. H. (2015). Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature, 526, 564-568.
Tauro, B. J., Greening, D. W., Mathias, R. A., Mathivanan, S., Ji, H., & Simpson, R. J. (2013). Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Molecular & Cellular Proteomics, 12(3), 587-598. https://doi.org/10.1074/mcp.M112.021303
Tay, C. Y., Muthu, M. S., Chia, S. L., Nguyen, K. T., Feng, S.-S., & Leong, D. T. (2016). Reality check for nanomaterial-mediated therapy with 3D biomimetic culture systems. Advanced Functional Materials, 26(23), 4046-4065. https://doi.org/10.1002/adfm.201600476
Tevis, K. M., Colson, Y. L., & Grinstaff, M. W. (2017). Embedded spheroids as models of the cancer microenvironment. Advanced Biosystems, 1(10), 1700083. https://doi.org/10.1002/adbi.201700083
ThermoFisher Scientific. (2019). 7/14/2019 Cancer spheroid and organoid eLearning course. Cell Analysis Guided Learning, Retrieved from www.thermofisher.com/us/en/home/life-science/cell-analysis/cell-analysis-learning-center/cell-analysis-resource-library/cell-analysis-guided-learning/cancer-spheroid-organoid-elearning-course.html
Thery, C., Boussac, M., Veron, P., Ricciardi-Castagnoli, P., Raposo, G., Garin, J., & Amigorena, S. (2001). Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles. Journal of Immunology, 166(12), 7309-7318. https://doi.org/10.4049/jimmunol.166.12.7309
Thippabhotla, S., Zhong, C., & He, M. (2019). 3D cell culture stimulates the secretion of in vivo like extracellular vesicles. Scientific Reports, 9(1), 13012. https://doi.org/10.1038/s41598-019-49671-3
Théry, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin-Smith, G. K., Ayre, D. C., Bach, J. M., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., … Jovanovic-Talisman, T. (2018). Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles, 7(1), 1535750. https://doi.org/10.1080/20013078.2018.1535750
Timmins, N. E., & Nielsen, L. K. (2007). Generation of multicellular tumor spheroids by the hanging-drop method. In H. Hauser, & M. Fussenegger (Eds.), Tissue engineering (pp. 141-151). Humana Press.
Tominaga, N., Kosaka, N., Ono, M., Katsuda, T., Yoshioka, Y., Tamura, K., Lötvall, J., Nakagama, H., & Ochiya, T. (2015). Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nature Communications, 6, 6716.
Trujillo, C. A., Gao, R., Negraes, P. D., Gu, J., Buchanan, J., Preissl, S., Wang, A., Wu, W., Haddad, G. G., Chaim, I. A., Domissy, A., Vandenberghe, M., Devor, A., Yeo, G. W., Voytek, B., & Muotri, A. R. (2019). Complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell, 25, 558-569.e7. https://doi.org/10.1016/j.stem.2019.08.002
Uccelli, A., Moretta, L., & Pistoia, V. (2008). Mesenchymal stem cells in health and disease. Nature Reviews Immunology, 8, 726-736. https://doi.org/10.1038/nri2395
U.S. Food and Drug Administration (FDA). (2019). U.S. Food and Drug Administration. Retrieved from www.fda.gov
Vader, P., Mol, E. A., Pasterkamp, G., & Schiffelers, R. M. (2016). Extracellular vesicles for drug delivery. Advanced Drug Delivery Reviews, 106, 148-156. https://doi.org/10.1016/j.addr.2016.02.006
Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology, 9(6), 654-659. https://doi.org/10.1038/ncb1596
Velasco, S., Kedaigle, A. J., Simmons, S. K., Nash, A., Rocha, M., Quadrato, G., Paulsen, B., Nguyen, L., Adiconis, X., Regev, A., Levin, J. Z., & Arlotta, P. (2019). Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature, 570(7762), 523-527. https://doi.org/10.1038/s41586-019-1289-x
Villasante, A., Marturano-Kruik, A., Ambati, S. R., Liu, Z., Godier-Furnemont, A., Parsa, H., Lee, B. W., Moore, M. A. S., & Vunjak-Novakovic, G. (2016). Recapitulating the size and cargo of tumor exosomes in a tissue-engineered model. Theranostics, 6(8), 1119-1130. https://doi.org/10.7150/thno.13944
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. (2016). Efficient production and enhanced tumor delivery of engineered extracellular vesicles. Biomaterials, 105, 195-205. https://doi.org/10.1016/j.biomaterials.2016.07.003
Weber, F., Kremer, C., Klinkhammer, M., Rasier, B., & Brock, M. (1994). Response of multicellular tumor spheroids to liposomes containing TNF-alpha. Journal of Neuro-Oncology, 18(3), 217-224.
Weil, B. R., Suzuki, G., Leiker, M. M., Fallavollita, J. A., & Canty, J. M. (2015). Comparative efficacy of intracoronary allogeneic mesenchymal stem cells and cardiosphere-derived cells in swine with hibernating myocardium. Circulation Research, 117(7), 634-644. https://doi.org/10.1161/CIRCRESAHA.115.306850
Whitford, W., & Guterstam, P. (2019). Exosome manufacturing status. Future Medicinal Chemistry, 11(10), 1225-1236. https://doi.org/10.4155/fmc-2018-0417
Wiklander, O. P. B., Brennan, M. Á., Lötvall, J., Breakefield, X. O., & El Andaloussi, S. (2019). Advances in therapeutic applications of extracellular vesicles. Science Translational Medicine, 11(492), eaav8521. https://doi.org/10.1126/scitranslmed.aav8521
Willis, G. R., Kourembanas, S., & Mitsialis, S. A. (2017). Toward exosome-based therapeutics: Isolation, heterogeneity, and fit-for-purpose potency. Frontiers in Cardiovascular Medicine, 4(63), https://doi.org/10.3389/fcvm.2017.00063
Xie, L., Mao, M., Zhou, L., Zhang, L., & Jiang, B. (2017). Signal factors secreted by 2D and spheroid mesenchymal stem cells and by cocultures of mesenchymal stem cells derived microvesicles and retinal photoreceptor neurons. Stem Cells International, 2017, 2730472-13. https://doi.org/10.1155/2017/2730472
Xu, R., Greening, D. W., Zhu, H.-J., Takahashi, N., & Simpson, R. J. (2016). Extracellular vesicle isolation and characterization: Toward clinical application. The Journal of Clinical Investigation, 126(4), 1152-1162. https://doi.org/10.1172/JCI81129
Xu, R., Rai, A., Chen, M., Suwakulsiri, W., Greening, D. W., & Simpson, R. J. (2018). Extracellular vesicles in cancer-Implications for future improvements in cancer care. Nature Reviews Clinical Oncology, 15(10), 617-638. https://doi.org/10.1038/s41571-018-0036-9
Yadid, M., Lind, J. U., Ardoña, H. A. M., Sheehy, S. P., Dickinson, L. E., Eweje, F., Bastings, M. M. C., Pope, B., O'Connor, B. B., Straubhaar, J. R., Budnik, B., Kleber, A. G., & Parker, K. K. (2020). Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip. Science Translational Medicine, 12(565), eaax8005. https://doi.org/10.1126/scitranslmed.aax8005
Yan, L., & Wu, X. (2020). Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity. Cell Biology and Toxicology, 36(2), 165-178. https://doi.org/10.1007/s10565-019-09504-5
Yang, B., Lui, C., Yeung, E., Matsushita, H., Jeyaram, A., Pitaktong, I., Inoue, T., Mohamed, Z., Ong, C. S., DiSilvestre, D., Jay, S. M., Tung, L., Tomaselli, G., Ma, C., & Hibino, N. (2019). A net mold-based method of biomaterial-free three-dimensional cardiac tissue creation. Tissue Engineering Part C: Methods, 25(4), 243-252. https://doi.org/10.1089/ten.tec.2019.0003
Yang, Y., Knight, R., Stephens, P., & Zhang, Y. (2020). Three-dimensional culture of oral progenitor cells: Effects on small extracellular vesicles production and proliferative function. Journal of Oral Pathology & Medicine, 49(4), 342-349. https://doi.org/10.1111/jop.12981
Yu, F., Hunziker, W., & Choudhury, D. (2019). Engineering microfluidic organoid-on-a-chip platforms. Micromachines, 10(3), 165. https://doi.org/10.3390/mi10030165
Yu, L. L., Zhu, J., Liu, J. X., Jiang, F., Ni, W. K., Qu, L. S., Ni, R. Z., Lu, C. H., & Xiao, M. B. (2018). A comparison of traditional and novel methods for the separation of exosomes from human samples. BioMed Research International, 2018, 3634563-3634569. https://doi.org/10.1155/2018/3634563
Yáñez-Mó, M., Siljander, P. R. M., Andreu, Z., Bedina Zavec, A., Borràs, F. E., Buzas, E. I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., Colás, E., Cordeiro-da Silva, A., Fais, S., Falcon-Perez, J. M., Ghobrial, I. M., Giebel, B., Gimona, M., Graner, M., Gursel, I., … De Wever, O. (2015). Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4(1), 27066. https://doi.org/10.3402/jev.v4.27066
Zha, Q. B., Yao, Y. F., Ren, Z. J., Li, X. J., & Tang, J. H. (2017). Extracellular vesicles: An overview of biogenesis, function, and role in breast cancer. Tumor Biology, 39(2), 1010428317691182. https://doi.org/10.1177/1010428317691182
Zhang, Y., Chopp, M., Zhang, Z. G., Katakowski, M., Xin, H., Qu, C., Ali, M., Mahmood, A., & Xiong, Y. (2017). Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury. Neurochemistry International, 111, 69-81. https://doi.org/10.1016/j.neuint.2016.08.003
Zuber, G., Dauty, E., Nothisen, M., Belguise, P., & Behr, J.-P. (2001). Towards synthetic viruses. Advanced Drug Delivery Reviews, 52(3), 245-253. https://doi.org/10.1016/S0169-409X(01)00213-7