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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Attermann, J 2003, 'Inaccuracy of INR measurements and suggestions for improved WHO guidelines for calibration of reference preparations – a statistical study', Journal of Thrombosis and Haemostasis, vol. 1, no. 3, pp. 537-44.

Miller, MR, Atkins, PR & Pedersen, OF 2003, 'Inadequate peak expiratory flow meter characteristics detected by a computerised explosive decompression device', Thorax, vol. 58, no. 5, pp. 411-416.

Bilde, T & Lubin, Y 2003, 'Inbreeding and the evolution of sociality - a comparative study of subsocial and social Stegodyphus spiders (Eresidae)', Paper presented at 4-9 August, St. Petersburg, Russia, 17/12/2010.

Kristensen, TN, Dahlgaard, J, Løvendahl, P & Loeschcke, V 2003, 'Inbreeding effects HSP70 in two species of Drosophila even at benign temperatures', International Congress of Genetics, Melbourne, Australia, 06/07/2003 - 11/07/2003.

Coupé, T, Smeets, V & Warzynski, F 2003 'Incentives in Economic Departments: Testing Tournaments?'.

Coupé, T, Smeets, V & Warzynski, F 2003 'Incentives, Sorting and Productivity along the Career - Evidence form a Sample of Top Economists'.

Fonager, K, Lindberg, J, Thulstrup, AM, Pedersen, L , Schønheyder, HC & Sørensen, HT 2003, 'Incidence and short-term prognosis of infective endocarditis in Denmark 1980-1997', Scandinavian Journal of Infectious Diseases, vol. 35, pp. 27-30.

Berntson, L, Andersson-Gäre, B, Fasth, A, Herlin, T, Kristinsson, J, Lahdenne, P, Marhaug, G, Nielsen, S & Pelkonen, P 2003, 'Incidence of juvenile idiopathic arthritis in the nordic countries: A population based study with special reference to the validity of the ILAR and EULAR criteria', J Rheumatol., vol. 30, pp. 2275-2282.

Berntson, L, Andersson Gäre, B, Fasth, A, Herlin, T, Kristinsson, J, Lahdenne, P, Marhaug, G, Nielsen, S, Pelkonen, P, Rygg, M & Nordic Study Group 2003, 'Incidence of juvenile idiopathic arthritis in the Nordic countries. A population based study with special reference to the validity of the ILAR and EULAR criteria', Journal of Rheumatology, vol. 30, no. 10, pp. 2275-82.

Hindhede, J , Kudahl, AB , Sørensen, JT & Knudsen, B 2003, Incidence of milk fever and description of applied control strategies for preventing milk fever/subclinical hypocalcaemia in large dairy herds. in Proc. 11th Int. Conf. Prod. Diseases in Farm Animals, 12-16 August 2001, Acta Vet. Scand. Suppl. 98. pp. 250-250, Incidence of milk fever and description of applied control strategies for preventing milk fever/subclinical hypocalcaemia in large dairy herds, 18/12/2010.

Perlick, C, Jensen, J, Overgaard, S & Søballe, K 2003, 'Incisional cellulitis after total hip arthroplasty: A case report', Acta Orthopaedica (Print Edition), vol. 74, no. 5, pp. 622-623.

Eriksson, TV 2003, Incitamentsystemer i dansk personaleledelse. in Kai Kristensen og Henrik D. Sørensen (red.) (ed.), Total Quality Management - Ledelse - Mennesker - Systemer - Resultater - Børsen Ledelseshåndbøger. Børsen Forum A/S, København, pp. Afsn. 5.2.

Dam, D & Christensen, S 2003, 'Including geophysical data in groundwater model inverse calibration', Groundwater, vol. 41, no. 2, pp. 178-189.

Andersen, I, Osler, M , Petersen, L, Grønbæk, M & Prescott, E 2003, 'Income and risk of ischaemic heart disease in men and women in a Nordic welfare country', International Journal of Epidemiology, vol. 32, no. 3, pp. 367-374. https://doi.org/10.1093/ije/dyg073

Kristensen, K 2003, Incomplete spilt-plots in variety trials - based on a-designs. in Biuletyn Oceny Odmian 31. pp. 7-17, Working Seminar on statistical methods in Variety Testing, Slup Wielka, Poland, 10/09/2003.

Andersen, MD, Jakobsen, HJ & Skibsted, J 2003, 'Incorporation of aluminum in the calcium silicate hydrate (C-S-H) of hydrated Portland cements: A high-field 27Al and 29Si MAS NMR investigation', Inorg. Chem., vol. 42, pp. 2280-2287. <http://pubs.acs.org/cgi-bin/article.cgi/inocaj/2003/42/i07/pdf/ic020607b.pdf>

Valle, M, Zavialov, A, Li, W, Stagg, SM, Sengupta, J, Nielsen, RC , Nissen, P, Harvey, SC, Ehrenberg, M & Frank, J 2003, 'Incorporation of aminoacyl-tRNA into the ribosome as seen by cryo-electron microscopy', Nat. Struct. Biol. ,vol. 10, pp. 899-906.

Fenton, RA, Chou, C-L, Ageloff, S, Brandt, W, Stokes, JB & Knepper, MA 2003, 'Increased collecting duct urea transporter expression in Dahl salt-sensitive rats', American Journal of Physiology: Renal Physiology, vol. 285, no. 1, pp. F143-51. https://doi.org/10.1152/ajprenal.00073.2003

Johansen, J, Tornøe, J, Møller, A & Johansen, TE 2003, 'Increased in vitro and in vivo transgene expression levels mediated through cis-acting elements', The Journal of Gene Medicine, vol. 5, pp. 1080-1089.

Lihn, AS, Richelsen, B , Pedersen, SB, Haugaard, SB, Rathje, GS, Madsbad, S & Andersen, O 2003, 'Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels', Am. J. Physiol. Endocrinol. Metab., vol. 285, no. 5.

Lihn, AS, Richelsen, B , Pedersen, SB, Haugaard, SB, Rathje, GS, Madsbad, S & Andersen, O 2003, 'Increased expression of TNF-α, IL-6, and IL-8 in HALS: Implications for reduced adiponectin expression and plasma levels', American Journal of Physiology - Endocrinology and Metabolism, vol. 285, no. 5 48-5, pp. E1072-E1080. https://doi.org/10.1152/ajpendo.00206.2003

Wegener, G, Bandpey, Z, Heiberg, IL, Mørk, A & Rosenberg, R 2003, 'Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat', Psychopharmacology (Berl), vol. 166, pp. 188-194.

Gravholt, CH , Vestergaard, P, Hermann, AP, Mosekilde, L, Brixen, K & Christiansen, JS 2003, 'Increased fracture rates in Turner's syndrome: a nationwide questionnaire survey', Clinical Endocrinology, vol. 59, no. 1, pp. 89-96.

Höllsberg, P, Hansen, HJ & Haahr, S 2003, 'Increased frequency of CD8+ T cells to immunodominant peptides within Epstein-Barr virus latent proteins in patients with multiple sclerosis', Clinical and Experimental Immunology, vol. 132, pp. 137-143.

Peura, TT, Rudiger, SR, Vajta, G & Walker, SK 2003, Increased in vitro development rates of sheep somatic cell nuclear transfer embryos produced by "reverse-order" zona-free method. in Proc. 29th Annual Conference IETS. pp. 280, Annual Conference of International Embryo Transfer Society, IETS, Auckland, New Zealand, 12/01/2003.

Danielsen, VO, Jørgensen, PF, Nissen, PM & Oksbjerg, N 2003, 'Increased maternal nutrition of sows has no beneficial effects on muscle fiber number or postnatal growth and has no impact on the meat quality of the offspring', Journal of Animal Science, vol. 81, pp. 3018-3027.

Thomsen, P, Kjeldsen, AM, Sørensen, JT & Houe, H 2003, Increased mortality among Danish dairy cows - a question of changed euthanisation policy? in Proc. 10th International Symposium of Veterinary Epidemiology and Economics (on CD-rom), Vina del Mar, Chile, Abstract 170. pp. 3-3, Increased mortality among Danish dairy cows - a question of changed euthanisation policy?, 18/12/2010.

Olsen, LH, Mortensen, K, Martinussen, T, Larsson, LI, Baandrup, U & Pedersen, HD 2003, 'Increased NADPH-Diaphorase activity in canine myxomatous mitral valve leaflets', J Comp Pathol, no. 129, pp. 20-130.

Anesio, AM & Granéli, W 2003, 'Increased photoreactivity of DOC by acidification: Implications for the carbon cycle in humic lakes', Limnology and Oceanography, vol. 48 (2), pp. 735 - 744.

Knudsen, ST, Foss, CH, Poulsen, PL , Andersen, NH, Mogensen, CE & Rasmussen, LM 2003, 'Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications', European Journal of Endocrinology, vol. 149, no. 1, pp. 39-42.

Knudsen, ST , Foss, CH , Poulsen, PL , Andersen, NH , Mogensen, CE & Rasmussen, LM 2003, 'Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications', European Journal of Endocrinology. Supplement, vol. 149, no. 1, pp. 39-42.

Lauszus, FF, Klebe, JG, Bek, T & Flyvbjerg, A 2003, 'Increased serum IGF-I during pregnancy is associated with progression of diabetic retinopathy', Diabetes, no. 52 (3), pp. 852-856.

Lauszus, FF, Klebe, JG, Bek, T & Flyvbjerg, A 2003, 'Increased serum IGF-I during pregnancy is associated with progression of diabetic retinopathy', Diabetes, vol. 52, no. 3, pp. 852-6.

Ivarsen, P, Frokiaer, J, Aagaard, NK, Hansen, EF, Bendtsen, F, Nielsen, S & Vilstrup, H 2003, 'Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis', Gut, vol. 52, no. 8, pp. 1194-1199.

Ivarsen, P, Frøkjær, J, Aagaard, NK, Hansen, EF, Bendtsen, F, Nielsen, S & Vilstrup, H 2003, 'Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis', Gut, vol. 52, pp. 1194-1199.

Poulsen, PL, Hansen, KW & Mogensen, CE 2003, 'Increase in nocturnal blood pressure and progression to microalbuminuria in diabetes', The New England Journal of Medicine, vol. 348, no. 3, pp. 260-264.

Poulsen, PL , Hansen, KW & Mogensen, CE 2003, 'Increase in nocturnal blood pressure and progression to microalbuminuria in diabetes', The New England Journal of Medicine, vol. 348, no. 3, pp. 260-4; author reply 260-4.

Cortet, J, Joffre, R, Elmholt, S & Krogh, PH 2003, 'Increasing species and trophic diversity of mesofauna affects fungal biomass, mesofauna community structure and organic matter decomposition processes', Biology and Fertility of Soils, vol. 37, pp. 302-312.

Carstensen, M, Thomsen, C & Hermansen, K 2003, 'Incremental area under response curve more accurately describes the triglyceride response to an oral fat load in both healthy and type-2 diabetic subjects', Metabolism, vol. 52, pp. 1034-1037.

Kristensen, TN, Sørensen, JG & Sørensen, AC 2003, 'Indavl og miljøstress - fra bananfluer til husdyr', Aktuel Naturvidenskab, vol. 5, pp. 17-20.

Warncke, E 2003, 'Indavl og undergang - om indavl i naturen', Aktuel Naturvidenskab, vol. 5, pp. 10-13.

Malchow-Møller, N & Würtz, A 2003, Indblik i statistik - En grundbog for videregående uddannelser. Gyldendal, Danmark.

Laustsen, CB & Wæver, O 2003, In Defense of Religion. Sacred Referent Objects for Securitization. in F Petito & P Patzopolos (eds), Religion in International Relations. The Return from Exile. Palgrave Macmillan, New York, pp. 147-180.

Studnitz, M , Jensen, MB & Pedersen, LJ 2003, In Denmark rooting material must be provided to all pigs from January 2003. in Proceedings of the 15th Nordic Symposium of the ISAE. pp. 12-12, 15th Nordic Symposium of the ISAE, 18/12/2010.

Hansen, S, Overgaard, J, Rose, C, Knoop, A, Lænkholm, A-V, Andersen, J , Sørensen, FB & Andreasen, P 2003, 'Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients', B J C, vol. 88, no. 1, pp. 102-108. https://doi.org/10.1038/sj.bjc.6600662

Lauridsen, O, Pedersen, BF & Pors, H 2003, In der Praxis: Arbejdsbog til skriftlig og mundtlig tysk. 4. edn, Aschehoug (Denmark), København.

Agarwal, PK, Arge, LA & Erickson, J 2003, 'Indexing Moving Points', Journal of Computer and System Sciences, vol. 66, Issue 1, pp. 207-243. https://doi.org/10.1016/S0022-0000(02)00035-1

Noe, E 2003, 'Indhold og troværdighed', Forskningsnytt, vol. 1, pp. 1-3.

Khair, T, Martens, K (ed.), Morris, P (ed.) & Warken, A (ed.) 2003, Indian English Poetry: Problems of Language and Prosody. in A World of Local Voices: Poetry in English Today. Königshausen, Würzburg, pp. 55-62.

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