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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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Alix, JJP, Neuwirth, C, Gelder, L, Burkhardt, C, Castro, J, de Carvalho, M, Gawel, M, Goedee, S, Grosskreutz, J, Lenglet, T, Moglia, C, Omer, T, Schrooten, M, Nandedkar, S, Stalberg, E, Barkhaus, PE, Furtula, J, van Dijk, JP, Baldinger, R, Costa, J, Otto, M, Sandberg, A & Weber, M 2019, 'Assessment of the reliability of the motor unit size index (MUSIX) in single subject “round-robin” and multi-centre settings', Clinical Neurophysiology, vol. 130, no. 5, pp. 666-674. https://doi.org/10.1016/j.clinph.2019.01.020
Borup, D 2019, 'Asset pricing model uncertainty', Journal of Empirical Finance, vol. 54, pp. 166-189. https://doi.org/10.1016/j.jempfin.2019.07.005
Nederstigt, C, Uitbeijerse, BS, Janssen, LGM, Corssmit, EPM, de Koning, EJP & Dekkers, OM 2019, 'Associated auto-immune disease in type 1 diabetes patients: a systematic review and meta-analysis', European Journal of Endocrinology, vol. 180, no. 2, pp. 135-144. https://doi.org/10.1530/EJE-18-0515
Worrich, A, Musat, N & Harms, H 2019, 'Associational effects in the microbial neighborhood', ISME Journal, vol. 13, no. 9, pp. 2143-2149. https://doi.org/10.1038/s41396-019-0444-6
Viola, TW, Schuch, JB, Rovaris, DL, Genovese, R, Tondo, L, Sanvicente-Vieira, B, Zaparte, A, Cupertino, RB, da Silva, BS, Bau, CHD & Grassi-Oliveira, R 2019, 'Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder', Journal of Neural Transmission, vol. 126, no. 12, pp. 1707-1711. https://doi.org/10.1007/s00702-019-02086-w
Hargreave, M, Jensen, A, Hansen, MK, Dehlendorff, C, Winther, JF, Schmiegelow, K & Kjær, SK 2019, 'Association between Fertility Treatment and Cancer Risk in Children', JAMA - Journal of the American Medical Association, vol. 322, no. 22, pp. 2203-2210. https://doi.org/10.1001/jama.2019.18037
Baumeister, SE, Schlesinger, S, Aleksandrova, K, Jochem, C, Jenab, M, Gunter, MJ, Overvad, K, Tjønneland, A, Boutron-Ruault, M-C, Carbonnel, F, Fournier, A, Kühn, T, Kaaks, R, Pischon, T, Boeing, H, Trichopoulou, A, Bamia, C, La Vecchia, C, Masala, G, Panico, S, Fasanelli, F, Tumino, R, Grioni, S, de Mesquita, BB, Vermeulen, R, May, AM, Borch, KB, Oyeyemi, SO, Ardanaz, E, Rodríguez-Barranco, M, López, MDC, Felez-Nobrega, M, Sonestedt, E, Ohlsson, B, Hemmingsson, O, Werner, M, Perez-Cornago, A, Ferrari, P, Stepien, M, Freisling, H, Tsilidis, KK, Ward, H, Riboli, E, Weiderpass, E & Leitzmann, MF 2019, 'Association between Physical Activity and Risk of Hepatobiliary Cancers: A Multinational Cohort Study', Journal of Hepatology, vol. 70, no. 5, pp. 885-892. https://doi.org/10.1016/j.jhep.2018.12.014
Mullee, A, Romaguera, D, Pearson-Stuttard, J, Viallon, V, Stepien, M, Freisling, H, Fagherazzi, G, Mancini, FR, Boutron-Ruault, M-C, Kühn, T, Kaaks, R, Boeing, H, Aleksandrova, K, Tjønneland, A, Halkjær, J, Overvad, K, Weiderpass, E, Skeie, G, Parr, CL, Quirós, JR, Agudo, A, Sánchez, M-J, Amiano, P, Cirera, L, Ardanaz, E, Khaw, K-T, Tong, TYN, Schmidt, JA, Trichopoulou, A, Martimianaki, G, Karakatsani, A, Palli, D, Agnoli, C, Tumino, R, Sacerdote, C, Panico, S, Bueno-de-Mesquita, B, Verschuren, WMM, Boer, JMA, Vermeulen, R, Ramne, S, Sonestedt, E, van Guelpen, B, Holgersson, PL, Tsilidis, KK, Heath, AK, Muller, D, Riboli, E, Gunter, MJ & Murphy, N 2019, 'Association Between Soft Drink Consumption and Mortality in 10 European Countries', JAMA Internal Medicine, vol. 179, no. 11, pp. 1479-1490. https://doi.org/10.1001/jamainternmed.2019.2478
Bauer, M, Glenn, T, Alda, M, Andreassen, OA, Angelopoulos, E, Ardau, R, Ayhan, Y, Baethge, C, Bauer, R, Baune, BT, Becerra-Palars, C, Bellivier, F, Belmaker, RH, Berk, M, Bersudsky, Y, Bicakci, Ş, Birabwa-Oketcho, H, Bjella, TD, Cabrera, J, Wo Cheung, EY, Del Zompo, M, Dodd, S, Donix, M, Etain, B, Fagiolini, A, Fountoulakis, KN, Frye, MA, Gonzalez-Pinto, A, Gottlieb, JF, Grof, P, Harima, H, Henry, C, Isometsä, ET, Janno, S, Kapczinski, F, Kardell, M, Khaldi, S, Kliwicki, S, König, B, Kot, TL, Krogh, R, Kunz, M, Lafer, B, Landén, M, Larsen, ER, Lewitzka, U, Licht, RW, Lopez-Jaramillo, C, MacQueen, G, Manchia, M, Marsh, W, Martinez-Cengotitabengoa, M, Melle, I, Meza-Urzúa, F, Ming, MY, Monteith, S, Morken, G, Mosca, E, Mozzhegorov, AA, Munoz, R, Mythri, SV, Nacef, F, Nadella, RK, Nery, FG, Nielsen, RE, O'Donovan, C, Omrani, A, Osher, Y, Sørensen, HØ, Ouali, U, Ruiz, YP, Pilhatsch, M, Pinna, M, da Ponte, FDR, Quiroz, D, Ramesar, R, Rasgon, N, Reddy, MS, Reif, A, Ritter, P, Rybakowski, JK, Sagduyu, K, Raghuraman, BS, Scippa, ÂM, Severus, E, Simhandl, C, Stackhouse, PW, Stein, DJ, Strejilevich, S, Subramaniam, M, Sulaiman, AH, Suominen, K, Tagata, H, Tatebayashi, Y, Tondo, L, Torrent, C, Vaaler, AE, Vares, E, Veeh, J, Vieta, E, Viswanath, B, Yoldi-Negrete, M, Zetin, M, Zgueb, Y & Whybrow, PC 2019, 'Association between solar insolation and a history of suicide attempts in bipolar I disorder', Journal of Psychiatric Research, vol. 113, no. June, pp. 1-9. https://doi.org/10.1016/j.jpsychires.2019.03.001
Rebello, K, Moura, LM, Xavier, G, Spindola, LM, Carvalho, CM, Hoexter, MQ, Gadelha, A, Picon, F, Pan, PM, Zugman, A, Grassi-Oliveira, R, Brietzke, E, Belangero, SI, Salum, GA, Rohde, LA, Miguel, EC, Bressan, R, Jackowski, A & Sato, JR 2019, 'Association between spontaneous activity of the default mode network hubs and leukocyte telomere length in late childhood and early adolescence', Journal of Psychosomatic Research, vol. 127, 109864. https://doi.org/10.1016/j.jpsychores.2019.109864
Bundgaard, JS, Østergaard, L, Gislason, G, Thune, JJ, Nielsen, JC, Haarbo, J, Videbæk, L, Olesen, LL, Thøgersen, AM, Torp-Pedersen, C, Pedersen, SS, Køber, L & Mogensen, UM 2019, 'Association between Type D personality and outcomes in patients with non-ischemic heart failure', Quality of Life Research, vol. 28, no. 11, pp. 2901-2908. https://doi.org/10.1007/s11136-019-02241-6
Besenbacher, S, Mailund, T, Vilhjálmsson, BJ & Schierup, MH 2019, Association mapping and disease: Evolutionary perspectives. in M Anisimova (ed.), Evolutionary genomics: Statistical and computational methods. 2 edn, Springer, Methods in Molecular Biology, vol. 1910, pp. 533-553. https://doi.org/10.1007/978-1-4939-9074-0_17
Qi, L, Huang, T & BIRTH-GENE (BIG) Study Working Group 2019, 'Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study', JAMA network open, vol. 2, no. 9, e1910915. https://doi.org/10.1001/jamanetworkopen.2019.10915
Edgren, G, Murphy, EL, Brambilla, DJ, Westlake, M, Rostgaard, K, Lee, C, Cable, RG, Triulzi, D, Bruhn, R, St Lezin, EM, Erikstrup, C, Ullum, H, Glynn, SA, Kleinman, S, Hjalgrim, H & Roubinian, NH 2019, 'Association of blood donor sex and prior pregnancy with mortality among red blood cell transfusion recipients', JAMA - Journal of the American Medical Association, vol. 321, no. 22, pp. 2183-2192. https://doi.org/10.1001/jama.2019.7084
Schönenberger, S, Hendén, PL, Simonsen, CZ, Uhlmann, L, Klose, C, Pfaff, JAR, Yoo, AJ, Sørensen, LH, Ringleb, PA, Wick, W, Kieser, M, Möhlenbruch, MA, Rasmussen, M, Rentzos, A & Bösel, J 2019, 'Association of General Anesthesia vs Procedural Sedation With Functional Outcome Among Patients With Acute Ischemic Stroke Undergoing Thrombectomy: A Systematic Review and Meta-analysis', JAMA: The Journal of the American Medical Association, vol. 322, no. 13, pp. 1283-1293. https://doi.org/10.1001/jama.2019.11455
Bai, D, Yip, BHK, Windham, GC, Sourander, A, Francis, R, Yoffe, R, Glasson, E, Mahjani, B, Suominen, A, Leonard, H, Gissler, M, Buxbaum, JD, Wong, K, Schendel, D, Kodesh, A, Breshnahan, M, Levine, SZ, Parner, ET, Hansen, SN, Hultman, C, Reichenberg, A & Sandin, S 2019, 'Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort', JAMA Psychiatry, vol. 76, no. 10, pp. 1035-1043. https://doi.org/10.1001/jamapsychiatry.2019.1411
Dam, V, van der Schouw, YT, Onland-Moret, NC, Groenwold, RHH, Peters, SAE, Burgess, S, Wood, AM, Chirlaque, M-D, Moons, KGM, Oliver-Williams, C, Schuit, E, Tikk, K, Weiderpass, E, Holm, M, Tjønneland, A, Kühn, T, Fortner, RT, Trichopoulou, A, Karakatsani, A, La Vecchia, C, Ferrari, P, Gunter, M, Masala, G, Sieri, S, Tumino, R, Panico, S, Boer, JMA, Verschuren, WMM, Salamanca-Fernández, E, Arriola, L, Moreno-Iribas, C, Engström, G, Melander, O, Nordendahl, M, Wennberg, P, Key, TJ, Colorado-Yohar, S, Matullo, G, Overvad, K, Clavel-Chapelon, F, Boeing, H, Quiros, JR, di Angelantonio, E, Langenberg, C, Sweeting, MJ, Riboli, E, Wareham, NJ, Danesh, J & Butterworth, A 2019, 'Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis', International Journal of Epidemiology, vol. 48, no. 4, dyz016, pp. 1275-1285. https://doi.org/10.1093/ije/dyz016
Kothari, M 2019, 'Association of orofacial dysfunction and dysphagia with oral intake in patients with brain injury', European Society for Swallowing Disorders, Vienna, Austria, 20/09/2019 - 21/09/2019.
Zheng, J-S, Imamura, F, Sharp, SJ, van der Schouw, YT, Sluijs, I, Gundersen, TE, Ardanaz, E, Boeing, H, Bonet, C, Gómez, JH, Dow, C, Fagherazzi, G, Franks, PW, Jenab, M, Kühn, T, Kaaks, R, Key, TJ, Khaw, K-T, Lasheras, C, Mokoroa, O, Mancini, FR, Nilsson, PM, Overvad, K, Panico, S, Palli, D, Rolandsson, O, Sieri, S, Salamanca-Fernández, E, Sacerdote, C, Spijkerman, AM, Stepien, M, Tjonneland, A, Tumino, R, Butterworth, AS, Riboli, E, Danesh, J, Langenberg, C, Forouhi, NG & Wareham, NJ 2019, 'Association of plasma vitamin D metabolites with incident type 2 diabetes: EPIC-InterAct case-cohort study', Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 4, pp. 1293-1303. https://doi.org/10.1210/jc.2018-01522
Musliner, KL, Mortensen, PB, McGrath, JJ, Suppli, NP, Hougaard, DM, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Andreassen, O, Pedersen, CB, Pedersen, MG, Mors, O, Nordentoft, M, Børglum, AD, Werge, T, Agerbo, E & Bipolar Disorder Working Group of the Psychiatric Genomics Consortium 2019, 'Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population', JAMA Psychiatry, vol. 76, no. 5, pp. 516-525. https://doi.org/10.1001/jamapsychiatry.2018.4166
Sun, S, Kuja-Halkola, R, Faraone, SV, D'Onofrio, BM, Dalsgaard, S, Chang, Z & Larsson, H 2019, 'Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder', J A M A Psychiatry, vol. 76, no. 11, pp. 1141-1149. https://doi.org/10.1001/jamapsychiatry.2019.1944
Fedirko, V, Jenab, M, Méplan, C, Jones, JS, Zhu, W, Schomburg, L, Siddiq, A, Hybsier, S, Overvad, K, Tjønneland, A, Omichessan, H, Perduca, V, Boutron-Ruault, M-C, Kühn, T, Katzke, V, Aleksandrova, K, Trichopoulou, A, Karakatsani, A, Kotanidou, A, Tumino, R, Panico, S, Masala, G, Agnoli, C, Naccarati, A, Bueno-de-Mesquita, B, Vermeulen, RCH, Weiderpass, E, Skeie, G, Nøst, TH, Lujan-Barroso, L, Quirós, JR, Huerta, JM, Rodríguez-Barranco, M, Barricarte, A, Gylling, B, Harlid, S, Bradbury, KE, Wareham, N, Khaw, K-T, Gunter, M, Murphy, N, Freisling, H, Tsilidis, K, Aune, D, Riboli, E, Hesketh, JE & Hughes, DJ 2019, 'Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status', Nutrients, vol. 11, no. 4, 935, pp. 935. https://doi.org/10.3390/nu11040935
Skipper, N, Gaulke, A, Sildorf, SM, Eriksen, TM, Nielsen, NF & Svensson, J 2019, 'Association of type 1 diabetes with standardized test scores of danish schoolchildren', JAMA - Journal of the American Medical Association, vol. 321, no. 5, pp. 484-492. https://doi.org/10.1001/jama.2018.21819
Barbu, MC, Zeng, Y, Shen, X, Cox, SR, Clarke, T-K, Gibson, J, Adams, MJ, Johnstone, M, Haley, CS, Lawrie, SM, Deary, IJ, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, McIntosh, AM & Whalley, HC 2019, 'Association of Whole-Genome and NETRIN1 Signaling Pathway-Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank', Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, vol. 4, no. 1, pp. 91-100. https://doi.org/10.1016/j.bpsc.2018.07.006
Santos Ferreira, DL, Hübel, C, Herle, M, Abdulkadir, M, Loos, RJF, Bryant-Waugh, R, Bulik, CM, De Stavola, BL, Lawlor, DA & Micali, N 2019, 'Associations between Blood Metabolic Profile at 7 Years Old and Eating Disorders in Adolescence: Findings from the Avon Longitudinal Study of Parents and Children', Metabolites, vol. 9, no. 9, 191. https://doi.org/10.3390/metabo9090191
Levinson, CA, Zerwas, SC, Brosof, LC, Thornton, LM, Strober, M, Pivarunas, B, Crowley, JJ, Yilmaz, Z, Berrettini, WH, Brandt, H, Crawford, S, Fichter, MM, Halmi, KA, Johnson, C, Kaplan, AS, La Via, M, Mitchell, J, Rotondo, A, Woodside, DB, Kaye, WH & Bulik, CM 2019, 'Associations between dimensions of anorexia nervosa and obsessive-compulsive disorder: An examination of personality and psychological factors in patients with anorexia nervosa', European Eating Disorders Review, vol. 27, no. 2, pp. 161-172. https://doi.org/10.1002/erv.2635
Dalgaard, F, Bondonno, NP, Murray, K, Bondonno, CP, Lewis, JR, Croft, KD, Kyrø, C, Gislason, G, Scalbert, A, Cassidy, A, Tjønneland, A, Overvad, K & Hodgson, JM 2019, 'Associations between habitual flavonoid intake and hospital admissions for atherosclerotic cardiovascular disease: a prospective cohort study', The Lancet. Planetary Health, vol. 3, no. 11, pp. e450-e459. https://doi.org/10.1016/S2542-5196(19)30212-8
Araghi, A, Martinez, CJ, Adamowski, J & Olesen, JE 2019, 'Associations between large-scale climate oscillations and land surface phenology in Iran', Agricultural and Forest Meteorology, vol. 278, 107682. https://doi.org/10.1016/j.agrformet.2019.107682
Hakim, O, Bonadonna, RC, Mohandas, C, Billoo, Z, Sunderland, A, Boselli, L, Alberti, KGMM, Peacock, JL, Umpleby, AM, Charles-Edwards, G, Amiel, SA & Goff, LM 2019, 'Associations between pancreatic lipids and β-cell function in black african and white european men with type 2 diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 4, pp. 1201-1210. https://doi.org/10.1210/jc.2018-01809
Løhmann, DJA, Asdahl, PH, Abrahamsson, J, Ha, S-Y, Jónsson, ÓG, Kaspers, GJL, Koskenvuo, M, Lausen, B, De Moerloose, B, Palle, J, Zeller, B, Sung, L & Hasle, H 2019, 'Associations between pretherapeutic body mass index, outcome, and cytogenetic abnormalities in pediatric acute myeloid leukemia', Cancer Medicine, vol. 8, no. 15, pp. 6634-6643. https://doi.org/10.1002/cam4.2554