{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:27:22Z","timestamp":1781886442588,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["602363"],"award-info":[{"award-number":["602363"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["322823"],"award-info":[{"award-number":["322823"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb4tm1Bor mice were intraperitoneally injected with either 100 \u00b5L of EVs (\u00b1 9.1 \u00d7 109 particles\/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.<\/jats:p>","DOI":"10.3390\/ijms21228874","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T11:50:34Z","timestamp":1606132234000},"page":"8874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Roberta","family":"Angioni","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica\u2014Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica\u2014Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-4931","authenticated-orcid":false,"given":"Vasanthy","family":"Vigneswara","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham; Centre for Liver and GI Research, Institute of Immunology and Immunotherapy, University of Birmingham; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Crescenzi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology\u2014DiSCOG, Gastroenterology and Multivisceral Transplant Unit, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Merino","sequence":"additional","affiliation":[{"name":"Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"S\u00e1nchez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica\u2014Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-7794","authenticated-orcid":false,"given":"Cristina","family":"Liboni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica\u2014Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Hoogduijn","sequence":"additional","affiliation":[{"name":"Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-3652","authenticated-orcid":false,"given":"Philip Noel","family":"Newsome","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham; Centre for Liver and GI Research, Institute of Immunology and Immunotherapy, University of Birmingham; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Muraca","sequence":"additional","affiliation":[{"name":"Fondazione Istituto di Ricerca Pediatrica Citt\u00e0 della Speranza, Padova, and Stem Cell and Regenerative Medicine Laboratory, Department of Women\u2019s and Children\u2019s Health, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-8941","authenticated-orcid":false,"given":"Francesco Paolo","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology\u2014DiSCOG, Gastroenterology and Multivisceral Transplant Unit, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Viola","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica\u2014Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1053\/j.gastro.2013.06.052","article-title":"Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management","volume":"145","author":"Eaton","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1056\/NEJMra1506330","article-title":"Primary Sclerosing Cholangitis","volume":"375","author":"Lazaridis","year":"2016","journal-title":"N. Eng. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.3748\/wjg.14.3350","article-title":"Etiopathogenesis of primary sclerosing cholangitis","volume":"14","author":"Chapman","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.jhep.2017.07.022","article-title":"Primary sclerosing cholangitis\u2014A comprehensive review","volume":"67","author":"Karlsen","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00281-009-0154-7","article-title":"The immunobiology of primary sclerosing cholangitis","volume":"31","author":"Aron","year":"2009","journal-title":"Semin. Immunopathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nri2395","article-title":"Mesenchymal stem cells in health and disease","volume":"8","author":"Uccelli","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13287-018-0816-2","article-title":"A pooled analysis of mesenchymal stem cell-based therapy for liver disease","volume":"9","author":"Zhao","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Borger, V., Bremer, M., Ferrer-Tur, R., Gockeln, L., Stambouli, O., Becic, A., and Giebel, B. (2017). Mesenchymal Stem\/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071450"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/pmic.201200373","article-title":"The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles","volume":"13","author":"Katsuda","year":"2013","journal-title":"Proteomics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev-pharmtox-061616-030146","article-title":"Stem Cell Extracellular Vesicles: Extended Messages of Regeneration","volume":"57","author":"Riazifar","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1002\/hep.30542","article-title":"Amelioration of Ductular Reaction by Stem Cell Derived Extracellular Vesicles in MDR2 knockout mice via let-7 microRNA","volume":"69","author":"McDaniel","year":"2019","journal-title":"Hepatology"},{"key":"ref_12","first-page":"1237","article-title":"Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis","volume":"145","author":"Mauad","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jhep.2005.06.025","article-title":"Mdr2 (Abcb4)-\/-mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes","volume":"43","author":"Popov","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1053\/gast.2002.35948","article-title":"Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles","volume":"123","author":"Fickert","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E968","DOI":"10.1073\/pnas.1521230113","article-title":"Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes","volume":"113","author":"Kowal","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1016\/j.bbagen.2016.07.028","article-title":"Methods for the physical characterization and quantification of extracellular vesicles in biological samples","volume":"1861","author":"Rupert","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1111\/liv.13402","article-title":"Enhanced liver fibrosis test predicts transplant-free survival in primary sclerosing cholangitis, a multi-centre study","volume":"37","author":"Farkkila","year":"2017","journal-title":"Liver Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.jhep.2014.02.006","article-title":"Characterization of animal models for primary sclerosing cholangitis (PSC)","volume":"60","author":"Fickert","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1002\/hep.28704","article-title":"Inhibition of mast cell-secreted histamine decreases biliary proliferation and fibrosis in primary sclerosing cholangitis Mdr2(-\/-) mice","volume":"64","author":"Jones","year":"2016","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1038\/s41374-018-0101-0","article-title":"Ursodeoxycholate inhibits mast cell activation and reverses biliary injury and fibrosis in Mdr2(-\/-) mice and human primary sclerosing cholangitis","volume":"98","author":"Meng","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rockey, D.C., Weymouth, N., and Shi, Z. (2013). Smooth muscle alpha actin (Acta2) and myofibroblast function during hepatic wound healing. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077166"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.dld.2004.11.009","article-title":"Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation","volume":"37","author":"Carpino","year":"2005","journal-title":"Dig. Liver Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e128060","DOI":"10.1172\/jci.insight.128060","article-title":"Mesenchymal stromal cell exosomes prevent and revert experimental pulmonary fibrosis through modulation of monocyte phenotypes","volume":"4","author":"Mansouri","year":"2019","journal-title":"JCI Insight"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Willis, G.R., Fernandez-Gonzalez, A., Reis, M., Mitsialis, S.A., and Kourembanas, S. (2018). Macrophage Immunomodulation: The Gatekeeper for Mesenchymal Stem Cell Derived-Exosomes in Pulmonary Arterial Hypertension?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092534"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1096\/fasebj.9.10.7542214","article-title":"Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers","volume":"9","author":"Collins","year":"1995","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a000034","DOI":"10.1101\/cshperspect.a000034","article-title":"The NF-kappaB family of transcription factors and its regulation","volume":"1","author":"Oeckinghaus","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40364-019-0156-0","article-title":"Novel insights into MSC-EVs therapy for immune diseases","volume":"7","author":"Lai","year":"2019","journal-title":"Biomark. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1089\/scd.2015.0008","article-title":"Mesenchymal Stem Cell Therapy for Autoimmune Disease: Risks and Rewards","volume":"24","author":"Munir","year":"2015","journal-title":"Stem Cells Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.jhep.2018.01.030","article-title":"Mesenchymal stromal cell therapy for liver diseases","volume":"68","author":"Alfaifi","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/leu.2012.202","article-title":"Encapsulated mesenchymal stem cells for in vivo immunomodulation","volume":"27","author":"Zanotti","year":"2013","journal-title":"Leukemia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/leu.2016.33","article-title":"Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1","volume":"30","author":"Zanotti","year":"2016","journal-title":"Leukemia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/s11033-019-04588-y","article-title":"Mesenchymal stem cell-based therapy for autoimmune diseases: Emerging roles of extracellular vesicles","volume":"46","author":"Rad","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by Extracellular Vesicles: Where We Are and Where We Need to Go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"G990","DOI":"10.1152\/ajpgi.00093.2010","article-title":"Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia","volume":"299","author":"Masyuk","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/cmi.2014.2","article-title":"The role of neutrophils in the development of liver diseases","volume":"11","author":"Xu","year":"2014","journal-title":"Cell Mol. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1478-3231.2011.02639.x","article-title":"Neutrophil to lymphocyte ratio: A new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease","volume":"32","author":"Alkhouri","year":"2012","journal-title":"Liver Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1111\/liv.12203","article-title":"Transgenic expression of human neutrophil peptide-1 enhances hepatic fibrosis in mice fed a choline-deficient, L-amino acid-defined diet","volume":"33","author":"Ibusuki","year":"2013","journal-title":"Liver Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/oby.20123","article-title":"Dietary modification dampens liver inflammation and fibrosis in obesity-related fatty liver disease","volume":"21","author":"Larter","year":"2013","journal-title":"Obesity"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rensen, S.S., Bieghs, V., Xanthoulea, S., Arfianti, E., Bakker, J.A., Shiri-Sverdlov, R., Hofker, M.H., Greve, J.W., and Buurman, W.A. (2012). Neutrophil-derived myeloperoxidase aggravates non-alcoholic steatohepatitis in low-density lipoprotein receptor-deficient mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052411"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Penz-Osterreicher, M., Osterreicher, C.H., and Trauner, M. (2011). Fibrosis in autoimmune and cholestatic liver disease. Best Pract. Res. Clin. Gastroenterol., 245\u2013258.","DOI":"10.1016\/j.bpg.2011.02.001"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s13770-017-0093-7","article-title":"Current Understanding of Stem Cell and Secretome Therapies in Liver Diseases","volume":"14","author":"Kim","year":"2017","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1172\/JCI66369","article-title":"Hepatic stellate cells in liver development, regeneration, and cancer","volume":"123","author":"Yin","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver inflammation and fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jcmgh.2018.01.003","article-title":"Neutrophil-Hepatic Stellate Cell Interactions Promote Fibrosis in Experimental Steatohepatitis","volume":"5","author":"Zhou","year":"2018","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1034\/j.1600-0528.2002.017412.x","article-title":"The liver as a site of T-cell apoptosis: Graveyard, or killing field?","volume":"174","author":"Crispe","year":"2000","journal-title":"Immunol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1182\/blood.V95.4.1362.004k17_1362_1369","article-title":"Migration of activated CD8(+) T lymphocytes to sites of viral infection does not require endothelial selectins","volume":"95","author":"Bartholdy","year":"2000","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1172\/JCI119468","article-title":"A minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature","volume":"99","author":"Wong","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.4049\/jimmunol.172.9.5222","article-title":"Passive and active mechanisms trap activated CD8+ T cells in the liver","volume":"172","author":"John","year":"2004","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S213","DOI":"10.1111\/j.1432-2277.1996.tb01612.x","article-title":"Expression of adhesion molecules and their ligands in liver allografts during cytomegalovirus (CMV) infection and acute rejection","volume":"9","author":"Lautenschlager","year":"1996","journal-title":"Transpl. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/hep.1840150216","article-title":"Vascular adhesion molecules in acute and chronic liver inflammation","volume":"15","author":"Volpes","year":"1992","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1023\/A:1006747106885","article-title":"Integrin alpha4beta1\/VCAM-1 pathway mediates primary adhesion of RAW117 lymphoma cells to hepatic sinusoidal endothelial cells under flow","volume":"17","author":"Papadimitriou","year":"1999","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/86539","article-title":"Functional alpha4-integrin: A newly identified pathway of neutrophil recruitment in critically ill septic patients","volume":"7","author":"Ibbotson","year":"2001","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1161\/CIRCULATIONAHA.111.090134","article-title":"Endothelial nuclear factor kappaB in obesity and aging: Is endothelial nuclear factor kappaB a master regulator of inflammation and insulin resistance?","volume":"125","author":"Kim","year":"2012","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrgastro.2010.213","article-title":"NF-kappaB in the liver--linking injury, fibrosis and hepatocellular carcinoma","volume":"8","author":"Luedde","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_56","first-page":"3951","article-title":"A study of regulatory effects of TLR4 and NF-kappaB on primary biliary cholangitis","volume":"23","author":"Yu","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yang, J., Liu, X.X., Fan, H., Tang, Q., Shou, Z.X., Zuo, D.M., Zou, Z., Xu, M., Chen, Q.Y., and Peng, Y. (2015). Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140551"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"L809","DOI":"10.1152\/ajplung.00358.2013","article-title":"Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation","volume":"306","author":"McAuley","year":"2014","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jprot.2017.07.012","article-title":"Proteomic analysis of the secretome of human bone marrow-derived mesenchymal stem cells primed by pro-inflammatory cytokines","volume":"166","author":"Maffioli","year":"2017","journal-title":"J. Proteom."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"153750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Thery","year":"2018","journal-title":"J. Extracell. Vesicles"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8874\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:36:18Z","timestamp":1760178978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":61,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21228874"],"URL":"https:\/\/doi.org\/10.3390\/ijms21228874","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]}}}