Exosomes

Exosomes are small membrane vesicles of endocytic origin secreted by most cell types in vitro. Cells continuously secrete a large number of microvesicles, exosomes and small molecules into the extracellular space. Exosomes have been shown to contain mRNA and miRNA and they are able to mediate communication between cells, by transport of RNA and proteins which can be functionalized in the recipient cell. The ability to transport bioactive cargoes, gives exosomes innate therapeutic potential as a natural drug carrier. Efficient techniques for loading drugs into exosomes to utilize the natural carrier capabilities of these vesicles remains to be elucidated.

Applications of Exosomes

The presence exosomes in blood, saliva, and urine paves the way for the possible application of exosomes as a diagnostic marker for diseases. Many diseases are difficult to detect by the methods and equipment available today and there is a growing demand for development of new non‐invasive methods to detect diseases in early stages. The use of exosomes as markers of disease is being investigated to cement their potential as a non-invasive diagnostic tool for early detection of many diseases, in particular cancers. This, however, relies on thorough characterisation of exosomes in both healthy and diseased states

An important factor to understanding the roles of exosomes is knowledge of their biodistribution. Currently, the number of publications describing the biodistribution of exosomes is limited. The main reason being the lack of a robust fluorescent label that can be visualised in vivo. Mapping the specific cell type derived exosomes can increase our knowledge on the roles of exosomes in the organism, as well as help to identify natural targeting systems.

Isolation, Characterisation and Fluorescent Labelling

The most common isolation protocol uses a differential centrifugation to fractionate cells, microvesicles, and exosomes, which are pelleted by ultracentrifugation. After vesicles are secreted from cells into the extracellular environment, it difficult to separate the different subpopulations of vesicles to obtain a pure sample. We have developed methods to optimise isolation and thorough characterisation procedures to obtain pure and well-characterised exosomes. Furthermore, we have developed a simple method for labelling of exosomes with a robust fluorescent label that can be visualised in vivo, allowing investigation of the biodistribution of different cell derived exosomes.

Collaborators:

Department of Clinical Medicine, Aarhus University Hospital, Denmark

Dan Peer, Department of Cell Research & Immunology, Tel Aviv University, Israel

Moein Moghimi, school of Medicine, Pharmacy and Health, Durham University, UK

Recent Publications

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Nielsen, SL & Nicolaisen, M 2003, 'Identification of two nucleotide sequence sub-groups within Potato mop-top Virus', Archives of Virology, vol. 148, pp. 381-388.

van der Keur, P, Ullum, M, Plougmann, MH & Iversen, BV 2003, Identification of vulnerable areas for pesticide leaching in Denmark. in A probabilistic modelling approach. EGS-AGU-EUG Joint Assembly. Geophysical Research Abstracts, no. EAE03-A-05743, vol. 5, Identification of vulnerable areas for pesticide leaching in Denmark, Nice, France, 06/04/2003.

Andersen, LD , Andersen, TT , Kruhøffer, M , Jensen, JL , Marcussen, N , Dutoit, SJH , Wolf, H & Ørntoft, TF 2003, 'Identifying distinct classes of bladder carcinoma using microarrays', Nature Genetics, vol. 33, pp. 90-96. https://doi.org/10.1038/ng1061

Dahl, CM & Gonzalez-Rivera, G 2003, 'Identifying Nonlinear Components by Random Fields in the US GNP Growth. Implications for the Shape of the Business Cycle', Studies in Nonlinear Dynamics and Econometrics (Online), vol. 7, no. 1.

Valbjørn, M 2003, 'Identitet og modernisering på Jordans dagsorden', Udenrigs, vol. 58, no. 2, pp. 56-66.

Jensen, KA, Utsunomiya, S, Glasius, M, Wåhlin, P , Palmgren, F & Ewing, RC 2003, 'Identity of transition and heavy metal nanoparticles in the urban outdoor and indoor atmosphere: Implications for health effect assessments', Nordic Conference of the Nordic Societies of Toxicology and Environmental Mutagenesis, Bornholm, Denmark, 15/06/2003 - 18/06/2003.

Madsen, MT 2003, 'Identity Work related to the use of MACintosh and PC in two research departments', Paper presented at Nordic Conference on Business Studies, Reykjavik, Iceland, 14/08/2003 - 16/08/2003.

Siiger, C 2003, Ideologisk ramme. Sygepleje på hjul - en del af Projekt Udenfor. Projekt Udenfor, København.

Sejer Jakobsen, H & Rebsdorf, SO 2003, Ideudvikling ved kreativ innovation. 1 edn, Gyldendal, København.

Jakobsen, HS & Rebsdorf, SO 2003, Ideudvikling ved kreativ Innovation: første danske bog forfattet i et samarbejde mellem et flyvende tæppe og en spyttende kamel. Gyldendal. <https://bibliotek.dk/da/work/870970-basis%3A24691985>

Mogensen, J, Kubo, T, Duque, M, Uribe, W, Shaw, A, Murphy, R, Gimeno, JR, Elliot, P & McKenna, WJ 2003, 'Idiopathic restrictive cardiomyopathy is part of the clinical expression of troponin I mutations', Journal of Clinical Investigation, vol. 111, no. 2, pp. 209-216.

Nielsen, NK 2003, 'Idræt og lokalhistorie - pejlinger og perspektiver i en dansk og nordisk kontekst', Idrætshistorisk Årbog 2002, pp. 11-26.

Evald, J (ed.) 2003, Idrætsjuristen. Djøf Forlag, København.

Ballisager, O 2003, Idrætspædagogisk årbog. Klim.

Vincken, J-P, Schols, HA, Oomen, RJFJ, McCann, MC, Ulvskov, P, Voragen, AGJ & Visser, RGF 2003, 'If homogalacturonan were a side chain of rhamnogalacturonan. I Implications for cell wall archictecture', Plant Physiology, vol. 132, pp. 1781-1789. <http://www.plantphysiol.org/cgi/content/full/132/4/1781?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=132&firstpage=1781&resourcetype=HWCIT>

Sørensen, BH 2003, 'If spare time didn't exit: - a future perspective on children's off-scholl virtual learning processes', Merz Wissenschaft.

Reinholdt, J & Husby, S 2003, IgA and Mucosal Homeostasis. in O Morteau (ed.), Oral Tolerance: The Response of the Intestinal Mucosa to Dietary Antigens. Eurekah, Boston, USA, pp. 82-113.

Madsen, JM 2003, 'I kapløb med tiden', Sfinx, vol. 26, no. 3, pp. 111-115.

Hansen, HP 2003, 'I kølvandet på Wilhjelmudvalget', Jæger, vol. 12, no. 2, pp. 36-38.

Kraglund, RA 2003, I krig og kærlighed - Middelalderens folkevise. in SA Sørensen (ed.), Ind i litteraturhistorien. Skolemedia A/S, Odense.

Dahl, B 2003, IKT baserte prøver i Norge. in Nordic meeting/conference/network meeting on testing and evaluation in mathematics; PRIM-gruppen, Stockholm Institute of Education, Sweden. 11-12 September 2003. Participants from universities and education ministries in Denmark, Finland, Iceland, Norway, and Sweden. By invitation only.. IKT baserte prøver i Norge, 17/12/2010.

Blomhøj, M 2003, IKT i matematikundervisningen: vilkår eller mulighed. in O Skovsmose & M Blomhøj (eds), Kan det virkelig passe?: om matematiklæring. L&R Uddannelse, København.

Kjeldsen, LPB 2003, IKT-udvikling med afsæt i teorien om den lærende organisation. in Skolen som lærende organisation - i teori og praksis. 1 udgave edn, Klim, Århus.

Jensen, HJL 2003, 'Ilden mellem himmel og jord', Dansk Teologisk Tidsskrift, no. 4, pp. 241-258.

Bazzichelli, T 2003, 'Il détournamento dei bit: Dalle pratiche situazioniste al cybersquatting', Avatar. Dislocazioni tra antropologia e comunicazione, no. 4.

Johansen, IE 2003, 'Ilex aquifolium L. den naturligt hjemmehørende kristtorn i Europa', Dansk Dendrologisk Aarsskrift, vol. 21, pp. 50-58.

Benediktsdottir, IS, Hintze, H , Petersen, JK & Wenzel, A 2003, 'Image quality of two solidstate and three photostimulable phosphor plate digital panoramic systems, and treatment planning of mandibular third molar removal', Dentomaxillofacial Radiology, vol. 32, pp. 39-44.

Borup, J 2003, 'Images of Asia', Kontakt, no. 4, pp. 14-17.

Markham, A 2003, 'Images of Internet: Tool, Place, Way of Being', Paper presented at AoIR 4.0, Association of Internet Researchers' Conference, Toronto, Canada, October 16-19, 2003, 17/12/2010.

Beek, MV 2003, Imaginaries of Ladakhi Modernity. in Ikke angivet. IATS, Tenth Seminar of the International Association for Tibetan Studies, Oxford, 6.-12. September 2003, United Kingdom, 17/12/2010.

Gjedde, A 2003, 'Imaging bones of contention.', Acta Orthopaedica (Print Edition), vol. 74, no. 6, pp. 631-2. https://doi.org/10.1080/00016470310018117

Puhakka, KB , Jurik, AG , Egund, N , Schiøttz-Christensen, B , Stengaard-Pedersen, K, Hansen, GVO & Christiansen, JV 2003, 'Imaging of sacroiliitis in early seronegative spondylarthropathy: Assessment of abnormalities by MR in comparison with radiography and CT', Acta Radiologica, vol. 44, no. 2, pp. 218-229.

Østergaard, L, Imaging system for obtaining quantative perfusion indices, Patent No. USP 6542769.

Bubandt, NO , Roepstorff, A & Kull, K (eds) 2003, Imagining Nature: Practices of Cosmology and Identity. Aarhus Universitetsforlag, Århus.

O'Brien, SG, Guilhot, F, Larsson, RA, Gathman, I, Baccarani, M, Cervantes, F, Cornelissen, JJ, Fischer, T, Hochhaus, A, Hughes, T, Lechner, K, Nielsen, JL, Reiffers, K, Rousselot, P, Saglio, G, Sheperd, J, Simonsson, B, Gratwohl, A, Goldman, JM, Kantarjian, H, Taylor, K, Verhoef, G, Capdeville, R & Druker, BJ 2003, 'Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia', N. Engl. J. Med., vol. 348, pp. 994-1004.

Verweij, J, van Oosterom, A, Blay, J-Y, Judson, I, Rodenhuis, S, van der Graaf, W, Radford, J, Le Cesne, A, Hogendoorn, PCW, di Paola, ED, Brown, M & Nielsen, OS 2003, 'Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study', European Journal of Cancer, vol. 39, no. 14, pp. 2006-11. https://doi.org/10.1016/S0959-8049(02)00836-5

Verweij, J, van Oosterrom, A, Blay, J-Y, Judson, I, Rodenhuis, S, Van der Graaf, W, Radford, J, Le Cesne, A, Hogendoorn, PCW, di Paola, ED, Brown, M & Nielsen, OS 2003, 'Imatinib (STI-571): an active agent for gastro-intestinal stromal tumours, but not yielding responses in other soft tissue sarcomas not selected for molecular target: Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study', European Journal of Cancer, vol. 39, no. 14, pp. 2006-2011.

Hervé, F, Millot, M-C, Rouchaud, J-C & Kragh-Hansen, U 2003, 'Immobilised copper(II) ion-affinity chromatography of natural mutants of human serum albumin and proalbumin', Chromatographia, no. 57, pp. 741-750.

Jorkov, AS, Donskov, F, Steiniche, T, Ternesten-Bratel, A, Naredi, P, Hellstrand, K & Hokland, M 2003, 'Immune response in blood and tumour tissue in patients with metastatic malignant melanoma treated with IL-2, IFN alpha and histamine dihydrochloride', Anticancer Research, no. 23, pp. 537-542.

Jørkov, AS, Donskov, F, Steiniche, T, Ternesten-Bratel, A, Naredi, P, Hellstrand, K & Hokland, M 2003, 'Immune response in blood and tumour tissue in patients with metastatic malignant melanoma treated with IL-2, IFN α and histamine dihydrochloride', Anticancer Research, vol. 23, pp. 537-542.

Pihakaski-Maunsbach, K, Vorum, H, Løcke, E-M, Garty, H, Karlish, SJD & Maunsbach, AB 2003, 'Immunocytochemical localization of Na,K-ATPase gamma subunit and CHIF in inner medulla of rat kidney', New York Academy of Sciences. Annals, vol. 986, pp. 401-409.

Danscher, G, Wang, Z, Kim, YK, Kim, SJ, Sun, Y & Jo, SM 2003, 'Immunocytochemical localization of zinc transporter 3 in the ependyma of the mouse spinal cord', Neurosci. Lett., vol. 342, no. 1-2, pp. 81-84.

Maddox-Hyttel, P, Alexopoulus, NI, Vajta, G, Lewis, I, Rogers, P, Cann, L, Callesen, H, Tveden-Nyborg, P & Trounson, A 2003, 'Immunohistochemical and ultrastructural characterization of the initial post-hatching development of bovine embryos', Reproduction, vol. 125, no. 4, pp. 607-623.

Agnholt, J , Kelsen, J, Schack, L & Sørensen, ES 2003, 'Immunostimulatory and modulatory effects of osteopontin, a milk derived protein with cytokine like properties, in intestinal T-lymphocytes', Gut, vol. 52, no. suppl VI, pp. 518-4.

Jensen, SS, Berkowicz, R, Hertel, O , Hvidberg, M, Kousgaard, U & Hansen, HS 2003, 'Impact Assessment System for Urban Air Pollution and Population Exposure', Airnet, Rome, Italy, 05/11/2003 - 07/11/2003.

Hansen, AS , Nielsen, TG, Levinsen, H, Madsen, SD, Thingstad, TF & Hansen, BW 2003, 'Impact of changing ice cover on pelagic productivity and food web structure in Disko Bay, West Greenland: a dynamic model approach', Deep-Sea Research Part I: Oceanographic Research Papers, vol. 50, pp. 171-187.

Gregersen, S , Thomsen, JL , Jeppesen, PB, Alstrup, KK, B., B , Pedersen, SB , Kristensen, K & Hermansen, K 2003, 'Impact of dietary FA and energy restriction on plasma leptin and ob gene expression in mice', Lipids, vol. 38, no. 5, pp. 513-517. https://doi.org/10.1007/s11745-003-1092-y

Møller, JE, Poulsen, SH, Søndergaard, E, Seward, JB, Appleton, CP & Egstrup, K 2003, 'Impact of early changes in left venticular filling pattern on long-term outcome after acute myocardial infarction', International Journal of Cardiology, vol. 89, no. 2-3, pp. 207-215.

Møller, JE , Poulsen, SH, Søndergaard, E, Seward, JB, Appleton, CP & Egstrup, K 2003, 'Impact of early changes in left ventricular filling pattern on long-term outcome after acute myocardial infarction', International Journal of Cardiology, vol. 89, no. 2-3, pp. 207-15. https://doi.org/10.1016/s0167-5273(02)00476-x

Andersen, NH, Poulsen, SH, Helleberg, K, Ivarsen, P, Knudsen, ST & Mogensen, CE 2003, 'Impact of essential hypertension and diabetes mellitus on left ventricular systolic and diastolic performance', European Journal of Echocardiography, vol. 4, no. 4, pp. 306-312.

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Lise Refstrup Linnebjerg Pedersen