{"entity": "researcher", "timestamp": "2026-08-09T08:02:36.460Z", "family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "affiliations": ["Krefting Research Centre, Institute of Medicine, University of Gothenburg, 40530, Gothenburg, Sweden. kyong-su.park@gu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18"}}, "publications": [{"entity": "publication", "iuid": "a572b67791f3483dbb7abb241e1938d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a572b67791f3483dbb7abb241e1938d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a572b67791f3483dbb7abb241e1938d3"}}, "title": "An Anti\u2010Myd88 Peptide Synergistically Enhances the Anti\u2010Inflammatory Effects of Extracellular Vesicles from Na\u00efve Umbilical Cord MSC or HEK293F CD24 Overexpressing Cells", "authors": [{"family": "Abas", "given": "Bur\u00e7in \u0130rem", "initials": "B\u0130", "orcid": "0000-0002-1018-5577", "researcher": {"href": "https://publications.scilifelab.se/researcher/941e021f937f43edab7eaed4003cbf7e.json"}}, {"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "Yu", "given": "Lijuan", "initials": "L", "orcid": "0000-0003-3558-3800", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b0b4ca8553144b19c236bc09c1c9b81.json"}}, {"family": "Wang", "given": "Yi", "initials": "Y", "orcid": "0000-0002-4954-6317", "researcher": {"href": "https://publications.scilifelab.se/researcher/272a124e437a4787a233f9010f1b097f.json"}}, {"family": "Gimona", "given": "Mario", "initials": "M", "orcid": "0000-0002-2242-2015", "researcher": {"href": "https://publications.scilifelab.se/researcher/b34548020ae94f38872dc7c79cd44b76.json"}}, {"family": "Park", "given": "Kyong\u2010su", "initials": "K", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal-article", "published": "2025-08-29", "journal": {"title": "Adv Materials Inter", "issn": "2196-7350", "issn-l": null}, "abstract": null, "doi": "10.1002/admi.202500252", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:25:34.023Z", "modified": "2025-11-05T13:25:34.577Z"}, {"entity": "publication", "iuid": "8a1c0d0e49ab4ddaaca2551db8330fbc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8a1c0d0e49ab4ddaaca2551db8330fbc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8a1c0d0e49ab4ddaaca2551db8330fbc"}}, "title": "Optimization of the Isolation Method for Large\u2010Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy", "authors": [{"family": "Ordouzadeh", "given": "Negar", "initials": "N"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Zimmer", "given": "Agnes", "initials": "A"}, {"family": "Tj\u00e4rnlund", "given": "Petra", "initials": "P"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "Park", "given": "Kyong\u2010Su", "initials": "K", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}], "type": "journal-article", "published": "2025-08-00", "journal": {"title": "Advanced Therapeutics", "issn": "2366-3987", "volume": "8", "issue": "8", "issn-l": null}, "abstract": null, "doi": "10.1002/adtp.202500084", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:58:52.094Z", "modified": "2025-11-05T13:58:52.148Z"}, {"entity": "publication", "iuid": "be2bf86eb5d64f5d95d391903ab5b1cf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be2bf86eb5d64f5d95d391903ab5b1cf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be2bf86eb5d64f5d95d391903ab5b1cf"}}, "title": "Development of Anti-Inflammatory Extracellular Vesicles by Surface Expression of Syndecan-4", "authors": [{"family": "Yu", "given": "Lijuan", "initials": "L", "orcid": "0000-0003-3558-3800", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b0b4ca8553144b19c236bc09c1c9b81.json"}}, {"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "Park", "given": "Kyong Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "posted-content", "published": "2025-07-09", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.07.05.663259", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T14:10:03.333Z", "modified": "2025-12-18T19:13:20.153Z"}, {"entity": "publication", "iuid": "e0be7d4528ff466fb50acb46d72fb250", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e0be7d4528ff466fb50acb46d72fb250.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e0be7d4528ff466fb50acb46d72fb250"}}, "title": "STING Agonist Drug Delivery by Bacterial Extracellular Vesicles Induces Synergistic Immuno-Oncology Responses and Efficient Inhibition of Tumour Growth.", "authors": [{"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "Ordouzadeh", "given": "Negar", "initials": "N"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "Deshmukh", "given": "Meghshree", "initials": "M"}, {"family": "Jin", "given": "Tao", "initials": "T"}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "14", "issue": "7", "pages": "e70117", "issn-l": "2001-3078"}, "abstract": "Bacterial extracellular vesicles are spherical, nanosized structures with lipid bilayer membranes and can suppress tumour growth in cancer models. However, the efficacy of some of these models is limited. One potential way to enhance their effects is by loading the bacterial vesicles with immunostimulatory molecules. We have here utilised synthetic bacterial vesicles (SyBV), previously shown to have anti-tumour effects but with reduced side effects. We hypothesized that loading SyBV with a STimulator of InterferoN Genes (STING) agonist can enhance anti-tumour effects. SyBV were generated from Escherichia coli membranes through cell breakdown induced by lysozyme and ionic stress. The produced nanovesicles encapsulated the STING agonist (SyBVSTING). SyBVSTING synergistically activated dendritic cells, leading to enhanced production of Interferon-\u03b2. Furthermore, in vivo experiments showed that immunisation with SyBVSTING synergistically suppresses melanoma and colon cancer growth by increasing the tumour infiltration of T cells. Intratumoural or subcutaneous injection of the SyBV resulted in retention in the tumour tissue over 24 h, but with some distribution to local lymph nodes. A toxicology experiment resulted in no histopathological concerns with SyBVSTING. These findings show that SyBV loaded with a STING agonist synergistically enhance anti-tumour immunity and may be a promising clinical immuno-oncology tool.", "doi": "10.1002/jev2.70117", "pmid": "40620049", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12230345"}], "notes": [], "created": "2025-11-05T13:54:01.033Z", "modified": "2025-11-05T13:54:01.099Z"}, {"entity": "publication", "iuid": "8d4a8412b91143359d590e01636497ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8d4a8412b91143359d590e01636497ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8d4a8412b91143359d590e01636497ae"}}, "title": "Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells.", "authors": [{"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Karimi", "given": "Nasibeh", "initials": "N", "orcid": "0000-0003-1499-6876", "researcher": {"href": "https://publications.scilifelab.se/researcher/14632eec875c42038aa0b6983e0ec107.json"}}, {"family": "Yu", "given": "Lijuan", "initials": "L", "orcid": "0000-0003-3558-3800", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b0b4ca8553144b19c236bc09c1c9b81.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2025-01-30", "journal": {"title": "J Nanobiotechnology", "issn": "1477-3155", "volume": "23", "issue": "1", "pages": "64", "issn-l": null}, "abstract": "Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor \"lymphocyte function-associated antigen-1\" (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18). The LFA-1 receptor was strongly overexpressed on the EVs released by the transfected cells. We further loaded these EVs with a therapeutic peptide, targeting myeloid differentiation primary response 88 (Myd88; EVMyd88), through a developed EV open-and-close procedure. Myd88 is a downstream common intracellular messenger for most TLR-receptors. EV expression of LFA-1 increases EV binding to ICAM-1-expressing cells, an effect that was dose-dependently inhibited by a specific neutralizing ICAM-1 antibody. Further, activated human endothelial cells treated with LFA-1 EVMyd88 had increased uptake of these EVs, resulting in dose-dependent inhibition of induced release of IL-8, presumably by targeting Myd88. We conclude that LFA-1-expressing EVMyd88 may be a candidate suitable for delivering therapeutic peptides in inflammatory diseases associated with TLR-activation.", "doi": "10.1186/s12951-025-03125-3", "pmid": "39885580", "labels": {"Glycoproteomics and MS Proteomics": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11780982"}, {"db": "pii", "key": "10.1186/s12951-025-03125-3"}], "notes": [], "created": "2025-10-23T13:06:45.347Z", "modified": "2025-11-05T13:48:02.553Z"}, {"entity": "publication", "iuid": "b017843641ad4057b8fde4e7fc40569e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b017843641ad4057b8fde4e7fc40569e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b017843641ad4057b8fde4e7fc40569e"}}, "title": "A Non-Centrifugation Method to Concentrate and Purify Extracellular Vesicles Using Superabsorbent Polymer Followed by Size Exclusion Chromatography.", "authors": [{"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2025-01-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "14", "issue": "1", "pages": "e70037", "issn-l": "2001-3078"}, "abstract": "Extracellular vesicles (EVs) can be isolated and purified from cell cultures and biofluids using different methodologies. Here, we explored a novel EV isolation approach by combining superabsorbent polymers (SAP) in a dialysis membrane with size exclusion chromatography (SEC) to achieve high concentration and purity of EVs without the use of ultracentrifugation (UC). Suspension HEK293 cells transfected with CD63 coupled with Thermo Luciferase were used to quantify the EV yield and purity. The 500 mL conditioned medium volume was initially reduced by pressure ultrafiltration, followed by UC, SAP or a centrifugal filter unit (CFU). Using either of these methods, the EVs were concentrated to a final volume of approximately 1 mL, with retained functionality. The yield, quantified by luciferase activity, was highest with UC (70%-80%), followed by SAP (60%-70%) and CFU (50%-60%). Further purification of the EVs was performed by iodixanol density cushion (IDC) or SEC (Sepharose CL-2B or 6B, in either 10 or 20 mL columns). Although the IDC and Sepharose CL-2B (10 mL) achieved the highest yields, the purity was slightly higher (30%) with IDC. In conclusion, combining SAP concentration with CL-2B SEC is an alternative and efficient way to isolate EVs without using UC.", "doi": "10.1002/jev2.70037", "pmid": "39840900", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11752139"}], "notes": [], "created": "2025-11-05T13:48:00.099Z", "modified": "2025-11-05T13:48:00.169Z"}, {"entity": "publication", "iuid": "46dfe0f573d5449e90d91f09b8e4c4b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/46dfe0f573d5449e90d91f09b8e4c4b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/46dfe0f573d5449e90d91f09b8e4c4b2"}}, "title": "Extracellular vesicles isolated from frozen and fresh human melanoma tissue are similar in purity and protein composition", "authors": [{"family": "D\u2019Arrigo", "given": "Daniele", "initials": "D"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "Urz\u00ec", "given": "Ornella", "initials": "O"}, {"family": "Park", "given": "Kyong Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Bagge", "given": "Roger Olofsson", "initials": "RO"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}], "type": "posted-content", "published": "2024-04-04", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2024.04.03.587936", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:03:52.819Z", "modified": "2025-12-18T19:28:19.475Z"}, {"entity": "publication", "iuid": "606035a2936d4b34b1717fa54273a2ac", "links": {"self": {"href": "https://publications.scilifelab.se/publication/606035a2936d4b34b1717fa54273a2ac.json"}, "display": {"href": "https://publications.scilifelab.se/publication/606035a2936d4b34b1717fa54273a2ac"}}, "title": "Immune-Associated Proteins Are Enriched in Lung Tissue-Derived Extracellular Vesicles during Allergen-Induced Eosinophilic Airway Inflammation.", "authors": [{"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Kishino", "given": "Yasunari", "initials": "Y"}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Shelke", "given": "Ganesh Vilas", "initials": "GV", "orcid": "0000-0001-5883-8082", "researcher": {"href": "https://publications.scilifelab.se/researcher/beeaee610fe341d79fa92f2f4f9a9683.json"}}, {"family": "Karimi", "given": "Nasibeh", "initials": "N"}, {"family": "Suzuki", "given": "Shintaro", "initials": "S"}, {"family": "Hovhannisyan", "given": "Lilit", "initials": "L"}, {"family": "R\u00e5dinger", "given": "Madeleine", "initials": "M", "orcid": "0000-0002-0652-7378", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8e9972bdb3b4d99a77a8c1fed528e21.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2021-04-29", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "22", "issue": "9", "issn-l": null}, "abstract": "Studying the proteomes of tissue-derived extracellular vesicles (EVs) can lead to the identification of biomarkers of disease and can provide a better understanding of cell-to-cell communication in both healthy and diseased tissue. The aim of this study was to apply our previously established tissue-derived EV isolation protocol to mouse lungs in order to determine the changes in the proteomes of lung tissue-derived EVs during allergen-induced eosinophilic airway inflammation. A mouse model for allergic airway inflammation was used by sensitizing the mice intraperitoneal with ovalbumin (OVA), and one week after the final sensitization, the mice were challenged intranasal with OVA or PBS. The animals were sacrificed 24 h after the final challenge, and their lungs were removed and sliced into smaller pieces that were incubated in culture media with DNase I and Collagenase D for 30 min at 37 \u00b0C. Vesicles were isolated from the medium by ultracentrifugation and bottom-loaded iodixanol density cushions, and the proteomes were determined using quantitative mass spectrometry. More EVs were present in the lungs of the OVA-challenged mice compared to the PBS-challenged control mice. In total, 4510 proteins were quantified in all samples. Among them, over 1000 proteins were significantly altered (fold change >2), with 614 proteins being increased and 425 proteins being decreased in the EVs from OVA-challenged mice compared to EVs from PBS-challenged animals. The associated cellular components and biological processes were analyzed for the altered EV proteins, and the proteins enriched during allergen-induced airway inflammation were mainly associated with gene ontology (GO) terms related to immune responses. In conclusion, EVs can be isolated from mouse lung tissue, and the EVs' proteomes undergo changes in response to allergen-induced airway inflammation. This suggests that the composition of lung-derived EVs is altered in diseases associated with inflammation of the lung, which may have implications in type-2 driven eosinophilic asthma pathogenesis.", "doi": "10.3390/ijms22094718", "pmid": "33946872", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8125637"}, {"db": "pii", "key": "ijms22094718"}], "notes": [], "created": "2023-03-07T14:36:41.337Z", "modified": "2024-01-16T13:46:30.562Z"}, {"entity": "publication", "iuid": "4461bb69c8ea443193eb31bbee80e195", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4461bb69c8ea443193eb31bbee80e195.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4461bb69c8ea443193eb31bbee80e195"}}, "title": "Mesenchymal stromal cell-derived nanovesicles ameliorate bacterial outer membrane vesicle-induced sepsis via IL-10.", "authors": [{"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Svennerholm", "given": "Kristina", "initials": "K"}, {"family": "Shelke", "given": "Ganesh V", "initials": "GV"}, {"family": "Bandeira", "given": "Elga", "initials": "E"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Jang", "given": "Su Chul", "initials": "SC"}, {"family": "Chandode", "given": "Rakesh", "initials": "R"}, {"family": "Gribonika", "given": "Inta", "initials": "I"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2019-08-01", "journal": {"title": "Stem Cell Res Ther", "issn": "1757-6512", "volume": "10", "issue": "1", "pages": "231", "issn-l": "1757-6512"}, "abstract": "Sepsis remains a source of high mortality in hospitalized patients despite proper antibiotic approaches. Encouragingly, mesenchymal stromal cells (MSCs) and their produced extracellular vesicles (EVs) have been shown to elicit anti-inflammatory effects in multiple inflammatory conditions including sepsis. However, EVs are generally released from mammalian cells in relatively low amounts, and high-yield isolation of EVs is still challenging due to a complicated procedure. To get over these limitations, vesicles very similar to EVs can be produced by serial extrusions of cells, after which they are called nanovesicles (NVs). We hypothesized that MSC-derived NVs can attenuate the cytokine storm induced by bacterial outer membrane vesicles (OMVs) in mice, and we aimed to elucidate the mechanism involved.\n\nNVs were produced from MSCs by the breakdown of cells through serial extrusions and were subsequently floated in a density gradient. Morphology and the number of NVs were analyzed by transmission electron microscopy and nanoparticle tracking analysis. Mice were intraperitoneally injected with Escherichia coli-derived OMVs to establish sepsis, and then injected with 2 \u00d7 10 9 NVs. Innate inflammation was assessed in peritoneal fluid and blood through investigation of infiltration of cells and cytokine production. The biodistribution of NVs labeled with Cy7 dye was analyzed using near-infrared imaging.\n\nElectron microscopy showed that NVs have a nanometer-size spherical shape and harbor classical EV marker proteins. In mice, NVs inhibited eye exudates and hypothermia, signs of a systemic cytokine storm, induced by intraperitoneal injection of OMVs. Moreover, NVs significantly suppressed cytokine release into the systemic circulation, as well as neutrophil and monocyte infiltration in the peritoneum. The protective effect of NVs was significantly reduced by prior treatment with anti-interleukin (IL)-10 monoclonal antibody. In biodistribution study, NVs spread to the whole mouse body and localized in the lung, liver, and kidney at 6 h.\n\nTaken together, these data indicate that MSC-derived NVs have beneficial effects in a mouse model of sepsis by upregulating the IL-10 production, suggesting that artificial NVs may be novel EV-mimetics clinically applicable to septic patients.", "doi": "10.1186/s13287-019-1352-4", "pmid": "31370884", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13287-019-1352-4"}, {"db": "pmc", "key": "PMC6676541"}], "notes": [], "created": "2020-01-23T16:10:40.078Z", "modified": "2021-06-16T14:54:54.314Z"}]}