Remyelinating effect driven by transferrin-loaded extracellular vesicles.
cuprizone deation model
exosomes
extracellular vesicles
intranasal administration
myelin
remyelination
transferrin
transferrin receptor 1
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
revised:
21
09
2023
received:
11
02
2023
accepted:
29
09
2023
pubmed:
20
10
2023
medline:
20
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
Extracellular vesicles (EVs) are involved in diverse cellular functions, playing a significant role in cell-to-cell communication in both physiological conditions and pathological scenarios. Therefore, EVs represent a promising therapeutic strategy. Oligodendrocytes (OLs) are myelinating glial cells developed from oligodendrocyte progenitor cells (OPCs) and damaged in chronic demyelinating diseases such as multiple sclerosis (MS). Glycoprotein transferrin (Tf) plays a critical role in iron homeostasis and has pro-differentiating effects on OLs in vivo and in vitro. In the current work, we evaluated the use of EVs as transporters of Tf to the central nervous system (CNS) through the intranasal (IN) route. For the in vitro mechanistic studies, we used rat plasma EVs. Our results show that EVTf enter OPCs through clathrin-caveolae and cholesterol-rich lipid raft endocytic pathways, releasing the cargo and exerting a pro-maturation effect on OPCs. These effects were also observed in vivo using the animal model of demyelination induced by cuprizone (CPZ). In this model, IN administered Tf-loaded EVs isolated from mouse plasma reached the brain parenchyma, internalizing into OPCs, promoting their differentiation, and accelerating remyelination. Furthermore, in vivo experiments demonstrated that EVs protected the Tf cargo and significantly reduced the amount of Tf required to induce remyelination as compared to soluble Tf. Collectively, these findings unveil EVs as functional nanocarriers of Tf to induce remyelination.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
338-361Subventions
Organisme : Fondo para la Investigación Científica y Tecnológica
ID : PICT 01798-2018
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Adamo, A. M., Paez, P. M., Escobar Cabrera, O. E., Wolfson, M., Franco, P. G., Pasquini, J. M., & Soto, E. F. (2006). Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin. Experimental Neurology, 198(2), 519-529. https://doi.org/10.1016/j.expneurol.2005.12.027
Allen Institute for Brain Science. (2004). Allen Mouse Brain Atlas [dataset]. Available from: mouse.brain-map.org
Allen Institute for Brain Science. (2011). Allen Reference Atlas - Mouse Brain [brain atlas]. Available from: atlas.brain-map.org
Bakhti, M., Winter, C., & Simons, M. (2011). Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. The Journal of Biological Chemistry, 286, 787-796. https://doi.org/10.1074/jbc.M110.190009
Bartlett, W. P., Li, X. S., & Connor, J. R. (1991). Expression of transferrin mRNA in the CNS of normal and jimpy mice. Journal of Neurochemistry, 57(1), 318-322. https://doi.org/10.1111/j.1471-4159.1991.tb02130.x
Basso, M., & Bonetto, V. (2016). Extracellular vesicles and a novel form of communication in the brain. Frontiers in Neuroscience, 31(10), 127. https://doi.org/10.3389/fnins.2016.00127
Bergles, D. E., & Richardson, W. D. (2015). Oligodendrocyte development and plasticity. Cold Spring Harbor Perspectives in Biology, 8(2), a020453. https://doi.org/10.1101/cshperspect.a020453
Bloch, B., Popovici, T., Levin, M. J., Tuil, D., & Kahn, A. (1985). Transferrin gene expression visualized in oligodendrocytes of the rat brain by using in situ hybridization and immunohistochemistry. Proceedings of the National Academy of Sciences of the United States of America, 82(19), 6706-6710. https://doi.org/10.1073/pnas.82.19.6706
Carden, T. R., Correale, J., Pasquini, J. M., & Pérez, M. J. (2019). Transferrin enhances microglial phagocytic capacity. Molecular Neurobiology, 56(9), 6324-6340. https://doi.org/10.1007/s12035-019-1519-0
Casella, G., Colombo, F., Finardi, A., Descamps, H., Ill-Raga, G., Spinelli, A., Podini, P., Bastoni, M., Martino, G., Muzio, L., & Furlan, R. (2018). Extracellular vesicles containing IL-4 modulate neuroinflammation in a mouse model of multiple sclerosis. Molecular Therapy, 26(9), 2107-2118. https://doi.org/10.1016/j.ymthe.2018.06.024
Choi, D., Montermini, L., Kim, D. K., Meehan, B., Roth, F. P., & Rak, J. (2018). The impact of oncogenic EGFRvIII on the proteome of extracellular vesicles released from glioblastoma cells. Molecular & Cellular Proteomics, 17(10), 1948-1964. https://doi.org/10.1074/mcp.RA118.000644
Correale, J., Halfon, M. J., Jack, D., Rubstein, A., & Villa, A. (2021). Acting centrally or peripherally: A renewed interest in the central nervous system penetration of disease-modifying drugs in multiple sclerosis. Multiple Sclerosis and Related Disorders, 56, 103264. https://doi.org/10.1016/j.msard.2021.103264
De Paula, M. L., Cui, Q. L., Hossain, S., Antel, J., & Almazan, G. (2014). The PTEN inhibitor bisperoxovanadium enhances myelination by amplifying IGF-1 signaling in rat and human oligodendrocyte progenitors. Glia, 62(1), 64-77. https://doi.org/10.1002/glia.22584
Escobar Cabrera, O. E., Bongarzone, E. R., Soto, E. F., & Pasquini, J. M. (1994). Single intracerebral injection of apotransferrin in young rats induces increased myelination. Developmental Neuroscience, 16(5-6), 248-254. https://doi.org/10.1159/000112116 PMID: 7768203.
Escobar Cabrera, O. E., Zakin, M. M., Soto, E. F., & Pasquini, J. M. (1997). Single intracranial injection of apotransferrin in young rats increases the expression of specific myelin protein mRNA. Journal of Neuroscience Research, 47(6), 603-608.
Espinosa de los Monteros, A., Kumar, S., Zhao, P., Huang, C. J., Nazarian, R., Pan, T., Scully, S., Chang, R., & de Vellis, J. (1999 Feb). Transferrin is an essential factor for myelination. Neurochemical Research, 24(2), 235-248. https://doi.org/10.1007/s11064-004-1826-2
Fais, S., O'Driscoll, L., Borras, F. E., Buzas, E., Camussi, G., Cappello, F., Carvalho, J., Cordeiro da Silva, A., Del Portillo, H., El Andaloussi, S., Ficko Trček, T., Furlan, R., Hendrix, A., Gursel, I., Kralj-Iglic, V., Kaeffer, B., Kosanovic, M., Lekka, M. E., Lipps, G., … Giebel, B. (2016). Evidence-based clinical use of nanoscale extracellular vesicles in nanomedicine. ACS Nano, 10(4), 3886-3899. https://doi.org/10.1021/acsnano.5b08015
Franklin, R. J., & Ffrench-Constant, C. (2008). Remyelination in the CNS: From biology to therapy. Nature Reviews. Neuroscience, 9(11), 839-855. https://doi.org/10.1038/nrn2480
Frühbeis, C., Fröhlich, D., Kuo, W. P., Amphornrat, J., Thilemann, S., Saab, A. S., Kirchhoff, F., Möbius, W., Goebbels, S., Nave, K. A., Schneider, A., Simons, M., Klugmann, M., Trotter, J., & Krämer-Albers, E. M. (2013). Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biology, 11, e1001604. https://doi.org/10.1371/journal.pbio.1001604
Galeano, C., Qiu, Z., Mishra, A., Farnsworth, S. L., Hemmi, J. J., Moreira, A., Edenhoffer, P., & Hornsby, P. J. (2018). The route by which intranasally delivered stem cells enter the central nervous system. Cell Transplantation, 27(3), 501-514. https://doi.org/10.1177/0963689718754561
Garcia, C., Paez, P., Davio, C., Soto, E. F., & Pasquini, J. M. (2004). Apotransferrin induces cAMP/CREB pathway and cell cycle exit in immature oligodendroglial cells. Journal of Neuroscience Research, 78(3), 338-346. https://doi.org/10.1002/jnr.20254
García, C. I., Paez, P., Soto, E. F., & Pasquini, J. M. (2003 Jun). Differential effects of apotransferrin on two populations of oligodendroglial cells. Glia, 42(4), 406-416. https://doi.org/10.1002/glia.10227
Garrick, M. D., Dolan, K. G., Horbinski, C., Ghio, A. J., Higgins, D., Porubcin, M., Moore, E. G., Hainsworth, L. N., Umbreit, J. N., Conrad, M. E., Feng, L., Lis, A., Roth, J. A., Singleton, S., & Garrick, L. M. (2003). DMT1: A mammalian transporter for multiple metals. Biometals, 16, 41-54.
Gibson, E. M., Purger, D., Mount, C. W., Goldstein, A. K., Lin, G. L., Wood, L. S., Inema, I., Miller, S. E., Bieri, G., Zuchero, J. B., Barres, B. A., Woo, P. J., Vogel, H., & Monje, M. (2014). Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science, 344(6183), 1252304. https://doi.org/10.1126/science.1252304
Guardia Clausi, M., Paez, P. M., Campagnoni, A. T., Pasquini, L. A., & Pasquini, J. M. (2012). Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event. Glia, 60(10), 1540-1554. https://doi.org/10.1002/glia.22374
Guardia Clausi, M., Pasquini, L. A., Soto, E. F., & Pasquini, J. M. (2010). Apotransferrin-induced recovery after hypoxic/ischaemic injury on myelination. ASN Neuro, 2(5), e00048. https://doi.org/10.1042/AN20100020
Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., Patel, T., Piroyan, A., Sokolsky, M., Kabanov, A. V., & Batrakova, E. V. (2015). Exosomes as drug delivery vehicles for Parkinson's disease therapy. Journal of Controlled Release, 207, 18-30. https://doi.org/10.1016/j.jconrel.2015.03.033
Herman, S., Fishel, I., & Offen, D. (2021). Intranasal delivery of mesenchymal stem cells-derived extracellular vesicles for the treatment of neurological diseases. Stem Cells, 39(12), 1589-1600. https://doi.org/10.1002/stem.3456
Illum, L. (2004). Is nose-to-brain transport of drugs in man a reality? The Journal of Pharmacy and Pharmacology, 56(1), 3-17. https://doi.org/10.1211/0022357022539
Jiang, F., Levison, S. W., & Wood, T. L. (1999). Ciliary neurotrophic factor induces expression of the IGF type I receptor and FGF receptor 1 mRNAs in adult rat brain oligodendrocytes. Journal of Neuroscience Research, 57(4), 447-457.
Kaiser, T., Allen, H. M., Kwon, O., Barak, B., Wang, J., He, Z., Jiang, M., & Feng, G. (2021). MyelTracer: A semi-automated software for myelin g-ratio quantification. eNeuro, 8(4). https://doi.org/10.1523/ENEURO.0558-20.2021
Kodali, M., Castro, O. W., Kim, D. K., Thomas, A., Shuai, B., Attaluri, S., Upadhya, R., Gitai, D., Madhu, L. N., Prockop, D. J., & Shetty, A. K. (2019). Intranasally administered human MSC-derived extracellular vesicles pervasively incorporate into neurons and microglia in both intact and status epilepticus injured forebrain. International Journal of Molecular Sciences, 21(1), 181. https://doi.org/10.3390/ijms21010181
Lai, C. P., Kim, E. Y., Badr, C. E., Weissleder, R., Mempel, T. R., Tannous, B. A., & Breakefield, X. O. (2015). Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nature Communications, 13(6), 7029. https://doi.org/10.1038/ncomms8029
Leitner, D. F., Todorich, B., Zhang, X., & Connor, J. R. (2015). Semaphorin4A is cytotoxic to oligodendrocytes, is elevated in microglia, and multiple sclerosis. ASN Neuro, 7(3), 175909141558750. https://doi.org/10.1177/1759091415587502
Leonard, A. K., Sileno, A. P., Brandt, G. C., Foerder, C. A., Quay, S. C., & Costantino, H. R. (2007). In vitro formulation optimization of intranasal galantamine leading to enhanced bioavailability and reduced emetic response in vivo. International Journal of Pharmaceutics, 335(1-2), 138-146. https://doi.org/10.1016/j.ijpharm.2006.11.013
Lochhead, J. J., & Thorne, R. G. (2012). Intranasal delivery of biologics to the central nervous system. Advanced Drug Delivery Reviews, 64(7), 614-628. https://doi.org/10.1016/j.addr.2011.11.002
Lopez-Verrilli, M. A., Picou, F., & Court, F. A. (2013). Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia, 61(11), 1795-1806. https://doi.org/10.1002/glia.22558
Loureiro, J. A., Gomes, B., Coelho, M. A., do Carmo Pereira, M., & Rocha, S. (2014). Targeting nanoparticles across the blood-brain barrier with monoclonal antibodies. Nanomedicine (London, England), 9(5), 709-722. https://doi.org/10.2217/nnm.14.27
Luan, X., Sansanaphongpricha, K., Myers, I., Chen, H., Yuan, H., & Sun, D. (2017). Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacologica Sinica, 38(6), 754-763. https://doi.org/10.1038/aps.2017.12
Lubetzki, C., & Stankoff, B. (2014). Demyelination in multiple sclerosis. Handbook of Clinical Neurology, 122, 89-99. https://doi.org/10.1016/B978-0-444-52001-2.00004-2
Ludwin, S. K. (1978). Central nervous system demyelination and remyelination in the mouse: An ultrastructural study of cuprizone toxicity. Laboratory Investigation, 39(6), 597-612.
Marimpietri, D., Petretto, A., Raffaghello, L., Pezzolo, A., Gagliani, C., Tacchetti, C., Mauri, P., Melioli, G., & Pistoia, V. (2013). Proteome profiling of neuroblastoma-derived exosomes reveal the expression of proteins potentially involved in tumor progression. PLoS One, 8(9), e75054. https://doi.org/10.1371/journal.pone.0075054
Marta, C. B., Davio, C., Pasquini, L. A., Soto, E. F., & Pasquini, J. M. (2002). Molecular mechanisms involved in the actions of apotransferrin upon the central nervous system: Role of the cytoskeleton and of second messengers. Journal of Neuroscience Research, 69(4), 488-496. https://doi.org/10.1002/jnr.10317
Marziali, L. N., Garcia, C. I., & Pasquini, J. M. (2015). Transferrin and thyroid hormone converge in the control of myelinogenesis. Experimental Neurology, 265, 129-141. https://doi.org/10.1016/j.expneurol.2014.12.021
Matsushima, G. K., & Morell, P. (2001). The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathology, 11(1), 107-116. https://doi.org/10.1111/j.1750-3639.2001.tb00385.x
Mattera, V. S., Pereyra Gerber, P., Glisoni, R., Ostrowski, M., Verstraeten, S. V., Pasquini, J. M., & Correale, J. D. (2020). Extracellular vesicles containing the transferrin receptor as nanocarriers of apotransferrin. Journal of Neurochemistry, 155(3), 327-338. https://doi.org/10.1111/jnc.15019
McCarthy, K. D., & de Vellis, J. (1980 Jun). Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. The Journal of Cell Biology, 85(3), 890-902. https://doi.org/10.1083/jcb.85.3.890
Mistry, A., Stolnik, S., & Illum, L. (2009). Nanoparticles for direct nose-to-brain delivery of drugs. International Journal of Pharmaceutics, 379(1), 146-157. https://doi.org/10.1016/j.ijpharm.2009.06.019
Moll, N. M., Hong, E., Fauveau, M., Naruse, M., Kerninon, C., Tepavcevic, V., Klopstein, A., Seilhean, D., Chew, L. J., Gallo, V., & Nait, O. B. (2013). SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis. Glia, 61(10), 1659-1672. https://doi.org/10.1002/glia.22547
Montecalvo, A., Larregina, A. T., Shufesky, W. J., Stolz, D. B., Sullivan, M. L., Karlsson, J. M., Baty, C. J., Gibson, G. A., Erdos, G., Wang, Z., Milosevic, J., Tkacheva, O. A., Divito, S. J., Jordan, R., Lyons-Weiler, J., Watkins, S. C., & Morelli, A. E. (2012). Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood, 119(3), 756-766. https://doi.org/10.1182/blood-2011-02-338004
Morelli, A. E., Larregina, A. T., Shufesky, W. J., Sullivan, M. L., Stolz, D. B., Papworth, G. D., Zahorchak, A. F., Logar, A. J., Wang, Z., Watkins, S. C., Falo, L. D., Jr., & Thomson, A. W. (2004). Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood, 104(10), 3257-3266. https://doi.org/10.1182/blood-2004-03-0824
Moyon, S., Dubessy, A. L., Aigrot, M. S., Trotter, M., Huang, J. K., Dauphinot, L., Potier, M. C., Kerninon, C., Melik Parsadaniantz, S., Franklin, R. J., & Lubetzki, C. (2015). Demyelination causes adult CNS progenitors to revert to an immature state and express immune cues that support their migration. The Journal of Neuroscience, 35(1), 4-20. https://doi.org/10.1523/JNEUROSCI.0849-14.2015
Mulcahy, L. A., Pink, R. C., & Carter, D. R. (2014). Routes and mechanisms of extracellular vesicle uptake. Journal of Extracellular Vesicles, 4, 3. https://doi.org/10.3402/jev.v3.24641
Paez, P. M., Marta, C. B., Moreno, M. B., Soto, E. F., & Pasquini, J. M. (2002). Apotransferrin decreases migration and enhances differentiation of oligodendroglial progenitor cells in an in vitro system. Developmental Neuroscience, 24(1), 47-58. https://doi.org/10.1159/000064945
Porro, C., Trotta, T., & Panaro, M. A. (2015). Microvesicles in the brain: Biomarker, messenger or mediator? Journal of Neuroimmunology, 15(288), 70-78. https://doi.org/10.1016/j.jneuroim.2015.09.006
Qiu, Y., Li, P., Zhang, Z., & Wu, M. (2021 Apr 27). Insights into Exosomal non-coding RNAs sorting mechanism and clinical application. Frontiers in Oncology, 11, 664904. https://doi.org/10.3389/fonc.2021.664904 Erratum in: Frontiers in Oncology 2021 Oct 11;11.
Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: Exosomes, microvesicles, and friends. The Journal of Cell Biology, 200(4), 373-383. https://doi.org/10.1083/jcb.201211138
Rasband, W. S., & ImageJ, U. S. (1997-2018). National Institutes of Health, Bethesda, Maryland, USA. https://imagej.nih.gov/ij/
Richter-Landsberg, C., & Heinrich, M. (1996). OLN-93: A new permanent oligodendroglia cell line derived from primary rat brain glial cultures. Journal of Neuroscience Research, 45(2), 161-173. https://doi.org/10.1002/(SICI)1097-4547(19960715)45:2<161::AID-JNR8>3.0.CO;2-8
Rosato-Siri, M. V., Marziali, L. N., Mattera, V., Correale, J., & Pasquini, J. M. (2021). Combination therapy of apo-transferrin and thyroid hormones enhances remyelination. Glia, 69(1), 151-164. https://doi.org/10.1002/glia.23891
Sáenz-Cuesta, M., Irizar, H., Castillo-Triviño, T., Muñoz-Culla, M., Osorio-Querejeta, I., Prada, A., Sepúlveda, L., López-Mato, M. P., López de Munain, A., Comabella, M., Villar, L. M., Olascoaga, J., & Otaegui, D. (2014). Circulating microparticles reflect treatment effects and clinical status in multiple sclerosis. Biomarkers in Medicine, 8(5), 653-661. https://doi.org/10.2217/bmm.14.9
Saint-Pol, J., Gosselet, F., Duban-Deweer, S., Pottiez, G., & Karamanos, Y. (2020). Targeting and crossing the blood-brain barrier with extracellular vesicles. Cell, 9(4), 851. https://doi.org/10.3390/cells9040851
Selmaj, I., Mycko, M. P., Raine, C. S., & Selmaj, K. W. (2017). The role of exosomes in CNS inflammation and their involvement in multiple sclerosis. Journal of Neuroimmunology, 15(306), 1-10. https://doi.org/10.1016/j.jneuroim.2017.02.002
Sen, M. K., Mahns, D. A., Coorssen, J. R., & Shortland, P. J. (2022). The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis. Glia, 70(7), 1215-1250. https://doi.org/10.1002/glia.24148
Silvestroff, L., Franco, P. G., & Pasquini, J. M. (2013). Neural and oligodendrocyte progenitor cells: Transferrin effects on cell proliferation. ASN Neuro, 5(1), e00107. https://doi.org/10.1042/AN20120075
Suzuki, K., & Kikkawa, Y. (1969). Status spongiosus of CNS and hepatic changes induced by cuprizone (biscyclohexanone oxalyldihydrazone). The American Journal of Pathology, 54(2), 307-325.
Thakur, A., Parra, D. C., Motallebnejad, P., Brocchi, M., & Chen, H. J. (2021). Exosomes: Small vesicles with big roles in cancer, vaccine development, and therapeutics. Bioactive Materials, 28(10), 281-294. https://doi.org/10.1016/j.bioactmat.2021.08.029
Théry, C., Ostrowski, M., & Segura, E. (2009). Membrane vesicles as conveyors of immune responses. Nature Reviews. Immunology, 9(8), 581-593. https://doi.org/10.1038/nri2567
Thompson, A. G., Gray, E., Heman-Ackah, S. M., Mäger, I., Talbot, K., Andaloussi, S. E., Wood, M. J., & Turner, M. R. (2016). Extracellular vesicles in neurodegenerative disease - pathogenesis to biomarkers. Nature Reviews. Neurology, 12(6), 346-357. https://doi.org/10.1038/nrneurol.2016.68
Todorich, B., Pasquini, J. M., Garcia, C. I., Paez, P. M., & Connor, J. R. (2009). Oligodendrocytes and myelination: The role of iron. Glia, 57(5), 467-478. https://doi.org/10.1002/glia.20784
van Niel, G., D'Angelo, G., & Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nature Reviews. Molecular Cell Biology, 19(4), 213-228. https://doi.org/10.1038/nrm.2017.125
Verderio, C., Muzio, L., Turola, E., Bergami, A., Novellino, L., Ruffini, F., Riganti, L., Corradini, I., Francolini, M., Garzetti, L., Maiorino, C., Servida, F., Vercelli, A., Rocca, M., Dalla Libera, D., Martinelli, V., Comi, G., Martino, G., Matteoli, M., & Furlan, R. (2012). Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Annals of Neurology, 72(4), 610-624. https://doi.org/10.1002/ana.23627
Verweij, F. J., Balaj, L., Boulanger, C. M., Carter, D. R. F., Compeer, E. B., D'Angelo, G., el Andaloussi, S., Goetz, J. G., Gross, J. C., Hyenne, V., Krämer-Albers, E. M., Lai, C. P., Loyer, X., Marki, A., Momma, S., Nolte-‘t Hoen, E. N. M., Pegtel, D. M., Peinado, H., Raposo, G., … van Niel, G. (2021). The power of imaging to understand extracellular vesicle biology in vivo. Nature Methods, 18, 1013-1026. https://doi.org/10.1038/s41592-021-01206-3
Wang, D., Gao, Y., & Yun, L. (2006). Study on brain targeting of raltitrexed following intranasal administration in rats. Cancer Chemotherapy and Pharmacology, 57(1), 97-104. https://doi.org/10.1007/s00280-005-0018-3
Westin, U., Piras, E., Jansson, B., Bergström, U., Dahlin, M., Brittebo, E., & Björk, E. (2005). Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents. European Journal of Pharmaceutical Sciences, 24(5), 565-573. https://doi.org/10.1016/j.ejps.2005.01.009
Wiklander, O. P., 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. I., Le Blanc, K., Macchiarini, P., Jungebluth, P., Wood, M. J., & Andaloussi, S. E. (2015). Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. Journal of Extracellular Vesicles, 20(4), 26316. https://doi.org/10.3402/jev.v4.26316
Wolburg, H., Wolburg-Buchholz, K., Sam, H., Horvát, S., Deli, M. A., & Mack, A. F. (2008). Epithelial and endothelial barriers in the olfactory region of the nasal cavity of the rat. Histochemistry and Cell Biology, 130, 127-140. https://doi.org/10.1007/s00418-008-0410-2
Yang, Z. L., Rao, J., Lin, F. B., Liang, Z. Y., Xu, X. J., Lin, Y. K., Chen, X. Y., Wang, C. H., & Chen, C. M. (2022). The role of exosomes and Exosomal noncoding RNAs from different cell sources in spinal cord injury. Frontiers in Cellular Neuroscience, 18(16), 882306. https://doi.org/10.3389/fncel.2022.882306
Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R. C., Ju, S., Mu, J., Zhang, L., Steinman, L., Miller, D., & Zhang, H. G. (2011). Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Molecular Therapy, 19(10), 1769-1779. https://doi.org/10.1038/mt.2011.164