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Baranov, Vladimir
Publikasjoner (10 av 31) Visa alla publikasjoner
Mincheva-Nilsson, L., Baranov, V., Nagaeva, O. & Dehlin, E. (2016). Isolation and characterization of exosomes from cultures of tissue explants and cell lines. Current Protocols in Immunology, 2016, 14.42.1-14.42.21
Åpne denne publikasjonen i ny fane eller vindu >>Isolation and characterization of exosomes from cultures of tissue explants and cell lines
2016 (engelsk)Inngår i: Current Protocols in Immunology, ISSN 1934-3671, Vol. 2016, s. 14.42.1-14.42.21Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Exosomes are specialized, nanometer-sized extracellular vesicles of endosomal origin actively secreted into the extracellular space by a variety of cells under normal and pathological conditions. Exosomes have recently emerged as important intercellular communicators and modulators of diverse mechanisms and cellular responses. Characterization of their composition and functionwill open possibilities for new diagnostic methods and promising therapeutic approaches based on nanobiology. This unit provides a standard isolation procedure for purification of exosomes based on density gradient ultracentrifugation with sucrose. The process of isolating exosomes relies on obtaining proper source fluids/supernatants as well as qualitative and quantitative assessment of the isolated vesicles. The methodological procedures here can be divided in three parts: (1) pre-isolation procedures aiming to obtain fluids containing exosomes, with a focus on protocols for organ explants and cell cultures; (2) a procedure for exosome isolation with several gradient alternatives; and (3) post-isolation procedures for estimating the purity and yield of the exosomal fraction.

sted, utgiver, år, opplag, sider
Wiley-Blackwell, 2016
Emneord
density ultracentrifugation, exosomes, Extracellular vesicles, flow cytometry, negative contrast staining, Organ explant culture, sucrose gradient, TEM
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-200033 (URN)10.1002/cpim.17 (DOI)27801511 (PubMedID)2-s2.0-85018275366 (Scopus ID)
Tilgjengelig fra: 2022-10-10 Laget: 2022-10-10 Sist oppdatert: 2022-10-10bibliografisk kontrollert
Mincheva-Nilsson, L. & Baranov, V. (2014). Placenta-derived exosomes and syncytiotrophoblast microparticles and their role in human reproduction: immune modulation for pregnancy success. American Journal of Reproductive Immunology, 72(5), 440-457
Åpne denne publikasjonen i ny fane eller vindu >>Placenta-derived exosomes and syncytiotrophoblast microparticles and their role in human reproduction: immune modulation for pregnancy success
2014 (engelsk)Inngår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 72, nr 5, s. 440-457Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

The syncytiotrophoblast (STB) of human placenta constitutively produces and secretes extracellular vesicles of different size, morphology and function that enter the maternal circulation, and participate in the maternal-fetal cross-talk during pregnancy. Syncytiotrophoblast-derived microvesicles/microparticles (STBM) are larger microvesicles (0.2-2m) shed by the apical plasma membrane of the STB as a result of cell activation and turnover. Simultaneously with the STBM shedding, the STB produces and secretes exosomes - nanosized (30-100/150nm) membrane-bound microvesicles that originate from the endosomal compartment. They convey cell-cell contact by proxy' transporting signals/packages of information between donor and recipient cells locally or/and at a distance. STBM and exosomes, delivered directly in the maternal blood surrounding the chorionic villi of the placenta, have contrasting biological functions. While the exosomes are immunosuppressive down regulating maternal immunity in pluripotent ways, the main effects of STBM on the maternal immune system are pro-inflammatory, immune activating, and pro-coagulant. Since both STBM and exosomes are present in the maternal circulation throughout normal pregnancy logical questions are what is the net effect of these vesicles on the maternal immune system and is this effect beneficial or detrimental to pregnancy. In this review, the current knowledge about placenta-derived extracellular vesicles with a main focus on exosomes is summarized and discussed. In a concluding remark, a hypothetical proposal on how STBM and exosomes might interact in pregnancy is discussed and a way to evaluate this interaction is suggested.

sted, utgiver, år, opplag, sider
Wiley-Blackwell, 2014
Emneord
exosomes, immunomodulation, microparticles, microvesicles, placenta, pregnancy, STBM
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-96493 (URN)10.1111/aji.12311 (DOI)000343731800002 ()2-s2.0-84908618253 (Scopus ID)
Tilgjengelig fra: 2014-12-01 Laget: 2014-11-21 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Lundholm, M., Schröder, M., Nagaeva, O., Baranov, V., Widmark, A., Mincheva-Nilsson, L. & Wikström, P. (2014). Prostate Tumor-Derived Exosomes Down-Regulate NKG2D Expression on Natural Killer Cells and CD8(+) T Cells: Mechanism of Immune Evasion. PLOS ONE, 9(9), e108925
Åpne denne publikasjonen i ny fane eller vindu >>Prostate Tumor-Derived Exosomes Down-Regulate NKG2D Expression on Natural Killer Cells and CD8(+) T Cells: Mechanism of Immune Evasion
Vise andre…
2014 (engelsk)Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 9, s. e108925-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Tumor-derived exosomes, which are nanometer-sized extracellular vesicles of endosomal origin, have emerged as promoters of tumor immune evasion but their role in prostate cancer (PC) progression is poorly understood. In this study, we investigated the ability of prostate tumor-derived exosomes to downregulate NKG2D expression on natural killer (NK) and CD8(+) T cells. NKG2D is an activating cytotoxicity receptor whose aberrant loss in cancer plays an important role in immune suppression. Using flow cytometry, we found that exosomes produced by human PC cells express ligands for NKG2D on their surface. The NKG2D ligand-expressing prostate tumor-derived exosomes selectively induced downregulation of NKG2D on NK and CD8(+) T cells in a dose-dependent manner, leading to impaired cytotoxic function in vitro. Consistent with these findings, patients with castration-resistant PC (CRPC) showed a significant decrease in surface NKG2D expression on circulating NK and CD8(+) T cells compared to healthy individuals. Tumor-derived exosomes are likely involved in this NKG2D downregulation, since incubation of healthy lymphocytes with exosomes isolated from serum or plasma of CRPC patients triggered downregulation of NKG2D expression in effector lymphocytes. These data suggest prostate tumor-derived exosomes as down-regulators of the NKG2D-mediated cytotoxic response in PC patients, thus promoting immune suppression and tumor escape.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-96829 (URN)10.1371/journal.pone.0108925 (DOI)000343671700191 ()2-s2.0-84931033158 (Scopus ID)
Tilgjengelig fra: 2014-12-05 Laget: 2014-12-03 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Skogberg, G., Gudmundsdottir, J., van der Post, S., Sandström, K., Bruhn, S., Benson, M., . . . Ekwall, O. (2013). Characterization of human thymic exosomes. PLOS ONE, 8(7), e67554
Åpne denne publikasjonen i ny fane eller vindu >>Characterization of human thymic exosomes
Vise andre…
2013 (engelsk)Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 8, nr 7, s. e67554-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Exosomes are nanosized membrane-bound vesicles that are released by various cell types and are capable of carrying proteins, lipids and RNAs which can be delivered to recipient cells. Exosomes play a role in intercellular communication and have been described to mediate immunologic information. In this article we report the first isolation and characterization of exosomes from human thymic tissue. Using electron microscopy, particle size determination, density gradient measurement, flow cytometry, proteomic analysis and microRNA profiling we describe the morphology, size, density, protein composition and microRNA content of human thymic exosomes. The thymic exosomes share characteristics with previously described exosomes such as antigen presentation molecules, but they also exhibit thymus specific features regarding surface markers, protein content and microRNA profile. Interestingly, thymic exosomes carry proteins that have a tissue restricted expression in the periphery which may suggest a role in T cell selection and the induction of central tolerance. We speculate that thymic exosomes may provide the means for intercellular information exchange necessary for negative selection and regulatory T cell formation of the developing thymocytes within the human thymic medulla.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-79252 (URN)10.1371/journal.pone.0067554 (DOI)000321341000055 ()2-s2.0-84879747232 (Scopus ID)
Tilgjengelig fra: 2013-09-05 Laget: 2013-08-13 Sist oppdatert: 2023-03-23bibliografisk kontrollert
Stenqvist, A.-C., Nagaeva, O., Baranov, V. & Mincheva-Nilsson, L. (2013). Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the fetus. Journal of Immunology, 191(11), 5515-5523
Åpne denne publikasjonen i ny fane eller vindu >>Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the fetus
2013 (engelsk)Inngår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 191, nr 11, s. 5515-5523Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Apoptosis is crucially important in mediating immune privilege of the fetus during pregnancy. We investigated the expression and in vitro apoptotic activity of two physiologically relevant death messengers, the TNF family members Fas ligand (FasL) and TRAIL in human early and term placentas. Both molecules were intracellularly expressed, confined to the late endosomal compartment of the syncytiotrophoblast, and tightly associated to the generation and secretion of placental exosomes. Using immunoelectron microscopy, we show that FasL and TRAIL are expressed on the limiting membrane of multivesicular bodies where, by membrane invagination, intraluminal microvesicles carrying membranal bioactive FasL and TRAIL are formed and released in the extracellular space as exosomes. Analyzing exosomes secreted from placental explant cultures, to our knowledge, we demonstrate for the first time that FasL and TRAIL are clustered on the exosomal membrane as oligomerized aggregates ready to form death-inducing signaling complex. Consistently, placental FasL-and TRAIL-carrying exosomes triggered apoptosis in Jurkat T cells and activated PBMC in a dose-dependent manner. Limiting the expression of functional FasL and TRAIL to exosomes comprise a dual benefit: 1) storage of exosomal FasL and TRAIL in multivesicular bodies is protected from proteolytic cleavage and 2) upon secretion, delivery of preformed membranal death molecules by exosomes rapidly triggers apoptosis. Our results suggest that bioactive FasL-and TRAIL-carrying exosomes, able to convey apoptosis, are secreted by the placenta and tie up the immunomodulatory and protective role of human placenta to its exosome-secreting ability.

sted, utgiver, år, opplag, sider
The American Association of Immunologists, 2013
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-84107 (URN)10.4049/jimmunol.1301885 (DOI)000327180600019 ()2-s2.0-84888367722 (Scopus ID)
Tilgjengelig fra: 2013-12-18 Laget: 2013-12-16 Sist oppdatert: 2023-03-23bibliografisk kontrollert
Hedberg, M. E., Moore, E. R., Svensson-Stadler, L., Hörstedt, P., Baranov, V., Hernell, O., . . . Hammarström, M.-L. (2012). Lachnoanaerobaculum a new genus in Lachnospiraceae; characterization of Lachnoanaerobaculum umeaense gen. nov., sp. nov., isolated from human small intestine, Lachnoanaerobaculum orale gen. nov., sp. nov., isolated from saliva and reclassification of Eubacterium saburreum (Prevot) Holdeman and Moore 1970 as Lachnoanaerobaculum saburreum comb. nov.. International Journal of Systematic and Evolutionary Microbiology, 62(11), 2685-2690
Åpne denne publikasjonen i ny fane eller vindu >>Lachnoanaerobaculum a new genus in Lachnospiraceae; characterization of Lachnoanaerobaculum umeaense gen. nov., sp. nov., isolated from human small intestine, Lachnoanaerobaculum orale gen. nov., sp. nov., isolated from saliva and reclassification of Eubacterium saburreum (Prevot) Holdeman and Moore 1970 as Lachnoanaerobaculum saburreum comb. nov.
Vise andre…
2012 (engelsk)Inngår i: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 62, nr 11, s. 2685-2690Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Two new obligately anaerobic Gram-positive, saccharolytic and non-proteolytic spore-forming bacilli (strain CD3:22 and N1) are described. Strain CD3:22 was isolated from a biopsy of the small intestine of a child with celiac disease and strain N1 from the saliva of a healthy young man. The cells of both strains were observed to be filamentous with lengths of approximately 5 to >20 µm, some of them curving and with swellings. The novel organisms produced H2S, NH3, butyric acid and acetic acid as major metabolic end products. Phylogenetic analyses, based on comparative 16S rRNA gene sequencing, revealed close relationships (98 % sequence similarity) between the two isolates, as well as the type strain of Eubacterium saburreum CCUG 28089T and four other Lachnospiraceae bacterium/E. saburreum-like organisms. This group of bacteria were clearly different from any of the 19 known genera in the family Lachnospiraceae. While Eubacterium spp. are reported to be non-spore-forming, reanalysis of E. saburreum CCUG 28089T confirmed that the bacterium, indeed, is able to form spores. Based on 16S rRNA gene sequencing, phenotypic and biochemical properties, CD3:22 (CCUG 58757T) and N1 (CCUG 60305T) represent new species of a new and distinct genus, named Lachnoanaerobaculum, in the family Lachnospiraceae [within the order Clostridiales, class Clostridia, phylum Firmicutes]. Strain CD3:22 is the type strain of the type species, Lachnoanaerobaculum umeaense gen. nov., sp. nov., of the proposed new genus. Strain N1 is the type strain of the species, Lachnoanaerobaculum orale gen. nov., sp. nov. Moreover, E. saburreum CCUG 28089T is reclassified as Lachnoanaerobaculum saburreum comb. nov.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-51168 (URN)10.1099/ijs.0.033613-0 (DOI)22228654 (PubMedID)2-s2.0-84868311393 (Scopus ID)
Forskningsfinansiär
EU, FP7, Seventh Framework Programme, 222720Swedish Research Council
Tilgjengelig fra: 2012-01-11 Laget: 2012-01-11 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Maguire, C. A., Balaj, L., Sivaraman, S., Crommentuijn, M. H. W., Ericsson, M., Mincheva-Nilsson, L., . . . Skog, J. (2012). Microvesicle-associated AAV Vector as a Novel Gene Delivery System. Molecular Therapy, 20(5), 960-971
Åpne denne publikasjonen i ny fane eller vindu >>Microvesicle-associated AAV Vector as a Novel Gene Delivery System
Vise andre…
2012 (engelsk)Inngår i: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 20, nr 5, s. 960-971Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Adeno-associated virus (AAV) vectors have shown remarkable efficiency for gene delivery to cultured cells and in animal models of human disease. However, limitations to AAV vectored gene transfer exist after intravenous transfer, including off-target gene delivery (e.g., liver) and low transduction of target tissue. Here, we show that during production, a fraction of AAV vectors are associated with microvesicles/exosomes, termed vexosomes (vector-exosomes). AAV capsids associated with the surface and in the interior of microvesicles were visualized using electron microscopy. In cultured cells, vexosomes outperformed conventionally purified AAV vectors in transduction efficiency. We found that purified vexosomes were more resistant to a neutralizing anti-AAV antibody compared to conventionally purified AAV. Finally, we show that vexosomes bound to magnetic beads can be attracted to a magnetized area in cultured cells. Vexosomes represent a unique entity which offers a promising strategy to improve gene delivery.

sted, utgiver, år, opplag, sider
New York: Nature Publishing Group, 2012
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-55673 (URN)10.1038/mt.2011.303 (DOI)000303484300012 ()2-s2.0-84860526022 (Scopus ID)
Tilgjengelig fra: 2012-05-29 Laget: 2012-05-28 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Hedlund, M., Nagaeva, O., Kargl, D., Baranov, V. & Mincheva-Nilsson, L. (2011). Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells. PLOS ONE, 6(2), e16899
Åpne denne publikasjonen i ny fane eller vindu >>Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells
Vise andre…
2011 (engelsk)Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 6, nr 2, s. e16899-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation of the high incidence of relapse and fatal outcome of many blood malignancies. In this report we have used Jurkat and Raji cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow cytometry we show that Jurkat and Raji cells constitutively express mRNA and protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and up-regulate the expression in a cell-line specific and stress-specific manner. Furthermore, we revealed by electron microscopy, immunoflow cytometry and western blot that these ligands were expressed and secreted on exosomes, nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. Interestingly, thermal and oxidative stress enhanced the exosome secretion generating more soluble NKG2D ligands that aggravated the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed.

Identifikatorer
urn:nbn:se:umu:diva-42832 (URN)10.1371/journal.pone.0016899 (DOI)21364924 (PubMedID)
Tilgjengelig fra: 2011-04-13 Laget: 2011-04-13 Sist oppdatert: 2021-06-14bibliografisk kontrollert
Hedlund, M., Nagaeva, O., Kargl, D., Baranov, V. & Mincheva-Nilsson, L. (2011). Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells. PLOS ONE, 6(2), Article ID e16899.
Åpne denne publikasjonen i ny fane eller vindu >>Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells
Vise andre…
2011 (engelsk)Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 6, nr 2, artikkel-id e16899Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation of the high incidence of relapse and fatal outcome of many blood malignancies. In this report we have used Jurkat and Raji cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow cytometry we show that Jurkat and Raji cells constitutively express mRNA and protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and up-regulate the expression in a cell-line specific and stress-specific manner. Furthermore, we revealed by electron microscopy, immunoflow cytometry and western blot that these ligands were expressed and secreted on exosomes, nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. Interestingly, thermal and oxidative stress enhanced the exosome secretion generating more soluble NKG2D ligands that aggravated the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed.

sted, utgiver, år, opplag, sider
Public Library of Science, 2011
Emneord
exosomes, NKG2D, MIC/ULBP, leukemia/lymphoma, oxidative stress, thermal stress, hyperthermia
HSV kategori
Forskningsprogram
immunologi
Identifikatorer
urn:nbn:se:umu:diva-37120 (URN)10.1371/journal.pone.0016899 (DOI)000287764100014 ()21364924 (PubMedID)2-s2.0-79952159254 (Scopus ID)
Merknad

Originally included in thesis in manuscript form with title "Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells". 

Tilgjengelig fra: 2010-10-20 Laget: 2010-10-20 Sist oppdatert: 2022-06-28bibliografisk kontrollert
Hedberg, M., Hammarström, M.-L., Hernell, O., Baranov, V., Wai, S. N., Moore, E. & Hammarström, S. (2010). Clostridiales bacterium CD3:22-an anaerobic spore-forming bacterium isolated from small intestine in a celiac disease patient.
Åpne denne publikasjonen i ny fane eller vindu >>Clostridiales bacterium CD3:22-an anaerobic spore-forming bacterium isolated from small intestine in a celiac disease patient
Vise andre…
2010 (engelsk)Rapport (Annet vitenskapelig)
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-35386 (URN)
Merknad
Kompletteras 2012-09Tilgjengelig fra: 2010-08-16 Laget: 2010-08-16 Sist oppdatert: 2018-06-08bibliografisk kontrollert
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