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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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.

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.

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 Heart Journal Cardiovascular Imaging, vol. 4, no. 4, pp. 306-12. https://doi.org/10.1016/s1525-2167(03)00034-9

Sanderson, H, Boudreau, TM, Mabury, SA & Solomon, KR 2003, 'Impact of perfluorooctanoic acid on the structure of the zooplankton community in indoor microcosms', Aquatic Toxicology, vol. 62, no. 3, pp. 227-234.

Lindi, V, Schwab, U, Louheranta, A, Kaakso, M, Vessby, B, Hermansen, K, Storlien, L, Riccardi, G, Rivellese, A & Uusitupa, MIJ 2003, 'Impact of the pro12ALA polymorphism of the PPAR-gamma-2 gene on serum triacylglycerol respons to N-3 fatty acid supplementation', Mol. Genet. Metab., vol. 79, pp. 52-60.

Jakobsen, TS, Hansen, PB, Jeppesen, E, Grønkjær, P & Søndergaard, M 2003, 'Impact of three-spined stickleback Gasterosteus aculeatus on zooplankton and chl a in shallow, eutrophic, brackish lakes', Mar. Ecol. Prog. Ser., vol. 262, pp. 277-284.

Jakobsen, TS, Hansen, PB, Jeppesen, E, Grønkjær, P & Søndergaard, M 2003, 'Impact of three-spined stickleback Gasterosteus aculeatus on zooplankton and chl a in shallow, eutrophic, brackish lakes', Marine Ecology Progress Series, vol. 262, pp. 277-284.

Wurzler, S, Simmel, M, Diehl, K, Hennig, T, Herrmann, H, Iinuma, Y, Lehmann, K, Massling, A, Stratmann, F, Wiedensohler, A, Zech, G, Zeromskiene, K, Posselt, R, Hungershöfer, K, Trautmann, T, O. Andreae, M, Chand, D, Dusek, U, P. Frank, G, Helas, G, S. Parmar, R, Schmid, O, Winterrath, T, Welling, M, Trentmann, J, Graf, H-F, Langmann, B, J. Nober, F & Textor, C 2003, Impact of vegetation fires on composition and circulation of the atmosphere (EFEU). in AFO 2000 : the German program on atmospheric research. vol. 5, pp. 14-17.

Niemann, T, Labouriau, R, Sorensen, HT, Thorsgaard, N & Nielsen, TT 2003, Impact on prognosis of regional different referral for coronary angiography after exercise testing: A population-based follow-up study. in Proc. XIX Nordic Congress of Cardiology. pp. 40, Nordic Congress of Cardiology, Odense, Denmark, 04/06/2003.

Christensen, PB, Glud, RN, Dalsgaard, T & Gillespie, P 2003, 'Impacts of longline mussel farming on oxygen and nitrogen dynamics and biological communities of coastal sediments', Aquaculture, vol. 218, pp. 567-588.

Nielsen, MF, Caumo, A, Chandramouli, V, Schumann, WC, Cobelli, C, Landau, BR, Vilstrup, H, Rizza, RA & Schmitz, O 2003, 'Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short term hypercortisolemia in healthy subjects', Am. J. Physiol., vol. 286, pp. 102-110.

Bacic, D, Capuano, P, Gisler, SM, Pribanic, S, Christensen, EI, Biber, J, Loffing, J, Kaissling, B, Wagner, CA & Murer, H 2003, 'Impaired PTH-induced endocytic down-regulation of the renal type IIa Na⁺/P_i-cotransporter in RAP deficient mice with reduced megalin expression', Pflügers Archiv. Eur. J. Physiol., vol. 446, pp. 475-484.

Schou, S, Holmstrup, P, Jørgensen, T, Skovgaard, LT, Stoltze, K, Hjørting-Hansen, E & Wenzel, A 2003, 'Implant surface preparation in the surgical treatment of experimental peri-implantitis with autogenous bone graft and ePTFE membrane in cynomolgus monkeys', Clinical Oral Implants Research, vol. 14, pp. 412-422.

Ringsted, C, Østergaard, D & van der Vleuten, CPM 2003, 'Implementation of a formal in-training assessment programme in anaesthesiology and preliminary results of acceptability', Acta Anaesthesiologica Scandinavica, vol. 47, no. 10, pp. 1196-203.

Thysen, I , Danfær, AC , Detlefsen, N & Jensen, AL 2003, Implementation of a mechanistic simulation model in Internet based decision support. in EFITA 2003 Conference. <Forlag uden navn>, pp. 167-172, Implementation of a mechanistic simulation model in Internet based decision support, Debrecen - Budapest, Hungary, 18/12/2010.

Lassen, P , Bøjer, OQ , Hansen, JG , Jensen, AL & Thysen, I 2003, Implementation of Internet based decision support systems in Estonia, Latvia, Lithuania and Poland. in EFITA 2003 Conference. <Forlag uden navn>, pp. 59-66, Implementation of Internet based decision support systems in Estonia, Latvia, Lithuania and Poland, Debrecen - Budapest, Hungary, 18/12/2010.

Lindén, B & Olesen, SE (eds) 2003, Implementation of precision farming in practical agriculture: Proc. Seminar on Implementation of Precision Farming in Practical Agriculture. DIAS Report, no. 100.

Koppel, M, Hansen, JG , Lassen, P, Turka, I, Bimsteine, G & Valskyte, A 2003, Implementation of the NegFry decision support system in Baltic countries in 1999-2002. in Proc. tth Workshop of an European network for development of an integrated control strategy of potato late blight. PPO-Special Report, no. 9, pp. 47-58, Implementation of the NegFry decision support system in Baltic countries in 1999-2002, Poznan, Poland, 18/12/2010.

Bliksted, VF & Bendix, S 2003, Implementering af kognitiv miljøterapi: Et pilotprojekt. Århus: Psykiatrisk Hospitals Trykkeri.

Arge, LA 2003, Implementing External Memory Algorithms and Data Structures. in Proceedings of 5th Workshop on Algorithm Engineering and Experiments. Society for Industrial and Applied Mathematics, Workshop on Algorithm Engineering and Experiments, Baltimore, United States, 11/01/2003.

Nielsen, TG, Iken, K (ed.) & Konar, B (ed.) 2003, Implementing the Microbial Food Web in the Arctic Pelagic Ecosystem: A Case Study from Disko Bay, Western Greenland. in K Iken & B Konar (eds), Proceedings of the Arctic Biodiversity Workshop. New Census of Marine Life Initiative: Alaska Sea Grant College Program M-26, April 11-14, 2003 . University of Alaska Fairbanks, pp. 151-152.

Bilde, T 2003, 'Implications of mate choice for inbreeding and the evolution of sociality in spiders', Paper presented at European Society of Evolutionary Biology. 9th Congress, 18-24 August, Leeds, England, 17/12/2010.

Clausen, JD, McIntosh, DB, Vilsen, B, Woolley, DG & Andersen, JP 2003, 'Importance of conserved N-domain residues Thr⁴⁴¹, Glu⁴⁴², Lys⁵¹⁵, Arg⁵⁶⁰, and Leu⁵⁶² of sarcoplasmic reticulum Ca²⁺-ATPase for MgATP binding and subsequent catalyticsteps. Plasticity of the nucleotide-binding site', Journal of Biological Chemistry, vol. 278, pp. 20245-20258.

Toustrup-Jensen, MS & Vilsen, B 2003, 'Importance of conserved Thr²¹⁴ in domain A of the Na⁺,K⁺-ATPase for stabilization of the phosphoryl transition state complex in E₂P phosphorylation', Journal of Biological Chemistry, vol. 278, pp. 11402-11410.

Freytag, PV & Bridges, E 2003, 'Importance of Market Conditions in B2B Relationships', Paper presented at ANZMAG Conference, 18/12/2010.

Hornekær, L, Baurichter, A, Petrunin, VV, Field, D & Luntz, A 2003, 'Importance of SurfaceMorphology in Interstellar H₂ Formation', Science, vol. 302, pp. 1943.

Christensen, FB , Laurberg, I & Bünger, CE 2003, 'Importance of the back-café concept to rehabilitation after lumbar spinal fusion: a randomized clinical study with a 2-year follow-up', Spine, vol. 28, no. 23, pp. 2561-9. https://doi.org/10.1097/01.BRS.0000097890.96524.A1

Toustrup-Jensen, MS & Vilsen, B 2003, 'Importance of Thr²¹⁴ in the conserved TGES sequence of the Na⁺,K⁺-ATPase for vanadate binding and hydrolysis of E₂P', New York Academy of Sciences. Annals, vol. 986, pp. 267-269.

Vilsen, B & Toustrup-Jensen, MS 2003, 'Importance of transmembrane segment M3 of Na⁺,K⁺-ATPase for control of conformational changes and the cytoplasmic entry pathway for Na⁺', New York Academy of Sciences. Annals, vol. 986, pp. 50-57.

Storgaard, A 2003, Importmodellen i Vridsløselille. Justitsministeriet, Direktoratet for Kriminalforsorgen, København.

Strand, J 2003, 'Imposex and intersex in prosobranch gastropods from Danish waters', Poster presented at SETAC Europe, 13th Annual Meeting, Hamburg, Germany, 27/04/2003 - 01/05/2003.

Elmholt, S & Haase, MS 2003, 'Improper handling of grain may result in high levels of Ochratoksin A', DARCOF enews, no. 2.

Rejnmark, L , Vestergaard, P , Heickendorff, L , Andreasen, F & Mosekilde, L 2003, 'Improved bone mineral density in postmenopausal women on long-term treatment with loop diuretics', Bone, vol. 32 Suppl 1.

Lerche, DB, Sørensen, PB & Brüggemann, R 2003, 'Improved Estimation of the Ranking Probabilities in Partial Orders Using Random Linear Extensions by Approximation of the Mutual Ranking Probability', Journal of Chemical Information and Modeling, vol. 43, no. 5, pp. 1471-1480.

Poulsen, K, Ennibi, O-K & Haubek, D 2003, 'Improved PCR for detection of the highly leukotoxic JP2 clone of Actinobacillus actinomycetemcomitans in subgingival plaque samples', Journal of Clinical Microbiology, vol. 41, pp. 4829-4832.

Thomsen, R, Fogel, GB & Krink, T 2003, Improvement of Clustal-Derived Sequence Alignments with Evolutionary Algorithms. in 2003 Congress on Evolutionary Computation. IEEE Press, pp. 1499-1507.

Breiting, S 2003, Improve teaching with learning stations: An example of a learning station for environmental education. <http://www.youthmeetingyouth.org/topics/environment/learningstation.htm>

Waiswa, CD, Mutetikka, D, Weisbjerg, MR , Hvelplund, T, Omaria, R & Beyunga, J 2003, Improving goat productivity using improved bucks among goat populations in Budadiri county - Sironko district. in Proceedings, LSRP Annual Scientific Workshop, Kampala 18-20 Marc. pp. 54-57, Improving goat productivity using improved bucks among goat populations in Budadiri county - Sironko district, 18/12/2010.

Rasmussen, TK & Krink, T 2003, 'Improving Hidden Markov Model Training for Multiple Sequence Alignment by a Particle Swarm Optimization - Evolutionary Algorithm Hybrid', BioSystems, vol. 72, pp. 5-17.

Brinch-Pedersen, H, Harzak, F, Gregersen, PL & Holm, PB 2003, Improving phosphate bio-availability in transgenic wheat (triticum aestivum L). in Proc. 7th International Congress on Plant Molecular Biology. pp. 10-71, International Congress on Plant Molecular Biology, Barcelona, Spain, 16/06/2003.

Liu, F, Andersen, MN & Jensen, CR 2003, Improving water use efficiency based on comparative sensitivity of soybean stomatal conductance and photosynthesis to soil drying. in S Kang, B Davies, L Shan & H Cai (eds), Water-Saving Agriculture and Sustainable Use of Water and Land Resources. Proceedings of International Conference. Volume I. pp. 33-41, Improving water use efficiency based on comparative sensitivity of soybean stomatal conductance and photosynthesis to soil drying, Yangling-Shaanxi, China, 26/10/2003.

Liu, FL, Andersen, MN & Jensen, CR 2003, 'Improving water-use efficiency based on comparative sensitivity of soybean stomatal conductance and photosynthesis to soil drying', Journal of Experimental Botany, vol. 54, no. Supplement 5, pp. i5-i5.

Munk, OL, Keiding, S & Bass, L 2003, 'Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation', Am. J. Physiol. Gastrointest. Liver Physiol., vol. 285, pp. 671-680.

Munk, OL , Keiding, S & Bass, L 2003, 'Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation.', American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 285, no. 4, pp. G671-80. https://doi.org/10.1152/ajpgi.00054.2003

Lehmann, H & Schjørring, JH 2003, Im Räderwerk des "real existierenden Sozialismus" Kirchen in Ostmittel- und Osteuropa von Stalin bis Gorbatschow. Wallstein Verlag, Göttingen.

Hansen, TH 2003, 'IMS-kongressen i Leuven 2002', Danish Yearbook of Musicology, vol. 30, pp. 96-99.

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