{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T21:52:17Z","timestamp":1769550737318,"version":"3.49.0"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,25]],"date-time":"2020-01-25T00:00:00Z","timestamp":1579910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AA025974"],"award-info":[{"award-number":["R21 AA025974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AA023626"],"award-info":[{"award-number":["R21 AA023626"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>During chronic liver injury, hepatic stellate cells (HSC) undergo activation and are the principal cellular source of collagenous scar. In this study, we found that activation of mouse HSC (mHSC) was associated with a 4.5-fold increase in extracellular vesicle (EV) production and that fibrogenic gene expression (CCN2, Col1a1) was suppressed in Passage 1 (P1; activated) mHSC exposed to EVs from Day 4 (D4; relatively quiescent) mHSC but not to EVs from P1 mHSC. Conversely, gene expression (CCN2, Col1a1, \u03b1SMA) in D4 mHSC was stimulated by EVs from P1 mHSC but not by EVs from D4 mHSC. EVs from Day 4 mHSC contained only 46 proteins in which histones and keratins predominated, while EVs from P1 mHSC contained 337 proteins and these were principally associated with extracellular spaces or matrix, proteasome, collagens, vesicular transport, metabolic enzymes, ribosomes and chaperones. EVs from the activated LX-2 human HSC (hHSC) line also promoted fibrogenic gene expression in D4 mHSC in vitro and contained 524 proteins, many of which shared identity or had functional overlap with those in P1 mHSC EVs. The activation-associated changes in production, function and protein content of EVs from HSC likely contribute to the regulation of HSC function in vivo and to the fine-tuning of fibrogenic pathways in the liver.<\/jats:p>","DOI":"10.3390\/cells9020290","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T07:41:11Z","timestamp":1580110871000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Dynamic Changes in Function and Proteomic Composition of Extracellular Vesicles from Hepatic Stellate Cells during Cellular Activation"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-6262","authenticated-orcid":false,"given":"Xinlei","family":"Li","sequence":"first","affiliation":[{"name":"Center for Clinical and Translational Research, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-7814","authenticated-orcid":false,"given":"Ruju","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1748-2504","authenticated-orcid":false,"given":"Sherri","family":"Kemper","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-6486","authenticated-orcid":false,"given":"David R","family":"Brigstock","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bpg.2011.02.005","article-title":"Mechanisms of hepatic fibrogenesis","volume":"25","author":"Lee","year":"2011","journal-title":"Best Pr. Res. Clin. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1002\/cphy.c120035","article-title":"Hepatic stellate cells and liver fibrosis","volume":"3","author":"Puche","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/cbin.10790","article-title":"Molecular interplays in hepatic stellate cells: Apoptosis, senescence, and phenotype reversion as cellular connections that modulate liver fibrosis","volume":"41","author":"Ramos","year":"2017","journal-title":"Cell Biol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic stellate cells as key target in liver fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.hbpd.2018.04.003","article-title":"Hepatic fibrosis: It is time to go with hepatic stellate cell-specific therapeutic targets","volume":"17","author":"Ezhilarasan","year":"2018","journal-title":"Hepatobiliary Pancreat Dis. Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mokdad, A.A., Lopez, A.D., Shahraz, S., Lozano, R., Mokdad, A.H., Stanaway, J., Murray, C.J., and Naghavi, M. (2014). Liver cirrhosis mortality in 187 countries between 1980 and 2010: A systematic analysis. BMC Med., 12.","DOI":"10.1186\/s12916-014-0145-y"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1177\/1756283X11413002","article-title":"Current status of novel antifibrotic therapies in patients with chronic liver disease","volume":"4","author":"Friedman","year":"2011","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1586\/17474124.2.6.803","article-title":"Advances in antifibrotic therapy","volume":"2","author":"Friedman","year":"2008","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.coph.2019.09.006","article-title":"New and emerging anti-fibrotic therapeutics entering or already in clinical trials in chronic liver diseases","volume":"49","author":"Lemoinne","year":"2019","journal-title":"Curr. Opin. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7629724","DOI":"10.1155\/2016\/7629724","article-title":"Clinical Advancements in the Targeted Therapies against Liver Fibrosis","volume":"2016","author":"Bansal","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cgh.2013.01.005","article-title":"Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies","volume":"11","author":"Rockey","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.1016\/S0168-8278(12)60008-7","article-title":"Anti-fibrotic therapy: Lost in translation?","volume":"56","author":"Schuppan","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.jhep.2015.02.039","article-title":"Hepatic fibrosis: Concept to treatment","volume":"62","author":"Trautwein","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1074\/jbc.275.4.2247","article-title":"Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury","volume":"275","author":"Friedman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrgastro.2017.71","article-title":"Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets","volume":"14","author":"Szabo","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"G194","DOI":"10.1152\/ajpgi.00216.2016","article-title":"Extracellular vesicles in liver diseases","volume":"312","author":"Maji","year":"2017","journal-title":"Am. J. Physiol. Gastrointest Liver Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nrgastro.2014.7","article-title":"The emerging roles of microvesicles in liver diseases","volume":"11","author":"Lemoinne","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1002\/hep.28814","article-title":"Extracellular vesicles in liver pathobiology: Small particles with big impact","volume":"64","author":"Hirsova","year":"2016","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/hepr.12794","article-title":"Emerging role of exosomes in liver physiology and pathology","volume":"47","author":"Cai","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3410\/B3-15","article-title":"Exosomes: Secreted vesicles and intercellular communications","volume":"3","author":"Thery","year":"2011","journal-title":"F1000 Biol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1535750","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"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.surg.2014.04.014","article-title":"Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver","volume":"156","author":"Charrier","year":"2014","journal-title":"Surgery"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/hep.26768","article-title":"Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery in exosomes from mouse or human hepatic stellate cells","volume":"59","author":"Chen","year":"2014","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s12079-017-0421-7","article-title":"Pathways of production and delivery of hepatocyte exosomes","volume":"12","author":"Chen","year":"2018","journal-title":"J. Cell Commun. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"G491","DOI":"10.1152\/ajpgi.00140.2015","article-title":"Suppression of fibrogenic signaling in hepatic stellate cells by Twist1-dependent microRNA-214 expression: Role of exosomes in horizontal transfer of Twist1","volume":"309","author":"Chen","year":"2015","journal-title":"Am. J. Physiol. Gastrointest Liver Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1016\/j.ajpath.2016.07.011","article-title":"Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p","volume":"186","author":"Chen","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Devhare, P.B., Sasaki, R., Shrivastava, S., Di Bisceglie, A.M., Ray, R., and Ray, R.B. (2017). Exosome-Mediated Intercellular Communication between Hepatitis C Virus-Infected Hepatocytes and Hepatic Stellate Cells. J. Virol., 91.","DOI":"10.1128\/JVI.00349-17"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/hep.28644","article-title":"Exosome-mediated activation of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by gammadelta T cells in liver fibrosis","volume":"64","author":"Seo","year":"2016","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jcmgh.2015.07.007","article-title":"Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-gamma","volume":"1","author":"Povero","year":"2015","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3710","DOI":"10.1038\/s41598-017-03389-2","article-title":"Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells","volume":"7","author":"Lee","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.jhep.2016.01.010","article-title":"Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers","volume":"64","author":"Lua","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1002\/1873-3468.12448","article-title":"Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are novel receptors for HSC-derived exosomes","volume":"590","author":"Chen","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3389\/fimmu.2016.00335","article-title":"Extracellular Vesicles Including Exosomes Regulate Innate Immune Responses to Hepatitis B Virus Infection","volume":"7","author":"Kouwaki","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.jhep.2015.11.020","article-title":"Alcohol stimulates macrophage activation through caspase-dependent hepatocyte derived release of CD40L containing extracellular vesicles","volume":"64","author":"Verma","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9991","DOI":"10.1038\/srep09991","article-title":"Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS","volume":"5","author":"Bala","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hirsova, P., Ibrahim, S.H., Krishnan, A., Verma, V.K., Bronk, S.F., Werneburg, N.W., Charlton, M.R., Shah, V.H., Malhi, H., and Gores, G.J. (2016). Lipid-induced Signaling Causes Release of Inflammatory Extracellular Vesicles from Hepatocytes. Gastroenterology.","DOI":"10.1053\/j.gastro.2015.12.037"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1194\/jlr.M063412","article-title":"Hepatocytes release ceramide-enriched pro-inflammatory extracellular vesicles in an IRE1alpha-dependent manner","volume":"57","author":"Kakazu","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"ra88","DOI":"10.1126\/scisignal.2004512","article-title":"Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells","volume":"6","author":"Povero","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.omtn.2019.01.006","article-title":"Exosomal Transmission of MicroRNA from HCV Replicating Cells Stimulates Transdifferentiation in Hepatic Stellate Cells","volume":"14","author":"Kim","year":"2019","journal-title":"Mol. Nucleic Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30684","DOI":"10.1074\/jbc.M115.671735","article-title":"Exosome Adherence and Internalization by Hepatic Stellate Cells Triggers Sphingosine 1-Phosphate-dependent Migration","volume":"290","author":"Wang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, X., Chen, R., Kemper, S., and Brigstock, D. (2019). Extracellular vesicles from hepatocytes are therapeutic for toxin-mediated fibrosis and gene expression in the liver. Front. Cell Dev. Biol.","DOI":"10.3389\/fcell.2019.00368"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6079642","DOI":"10.1155\/2018\/6079642","article-title":"Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl4-Induced Liver Injury through Antioxidant Effect","volume":"2018","author":"Jiang","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1089\/scd.2012.0395","article-title":"Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis","volume":"22","author":"Li","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Qu, Y., Zhang, Q., Cai, X., Li, F., Ma, Z., Xu, M., and Lu, L. (2017). Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J. Cell Mol. Med.","DOI":"10.1111\/jcmm.13170"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9330","DOI":"10.1002\/jcp.26413","article-title":"Extracellular vesicles derived from human embryonic stem cell-MSCs ameliorate cirrhosis in thioacetamide-induced chronic liver injury","volume":"233","author":"Mardpour","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3212643","DOI":"10.1155\/2018\/3212643","article-title":"Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats","volume":"2018","author":"Ohara","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Povero, D., Pinatel, E.M., Leszczynska, A., Goyal, N.P., Nishio, T., Kim, J., Kneiber, D., de Araujo Horcel, L., Eguchi, A., and Ordonez, P.M. (2019). Human induced pluripotent stem cell-derived extracellular vesicles reduce hepatic stellate cell activation and liver fibrosis. JCI Insight, 5.","DOI":"10.1172\/jci.insight.125652"},{"key":"ref_50","first-page":"98","article-title":"Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt\/beta-catenin pathway","volume":"10","author":"Rong","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bruno, S., Pasquino, C., Herrera Sanchez, M.B., Tapparo, M., Figliolini, F., Grange, C., Chiabotto, G., Cedrino, M., Deregibus, M.C., and Tetta, C. (2019). HLSC-Derived Extracellular Vesicles Attenuate Liver Fibrosis and Inflammation in a Murine Model of Non-alcoholic Steatohepatitis. Mol. Ther.","DOI":"10.1016\/j.ymthe.2019.10.016"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1461505","DOI":"10.1080\/20013078.2018.1461505","article-title":"Therapeutic effects of serum extracellular vesicles in liver fibrosis","volume":"7","author":"Chen","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_53","first-page":"409","article-title":"Fibronectin dependent upregulation of matrix metalloproteinases in hepatic stellate cells","volume":"40","author":"Pranitha","year":"2003","journal-title":"Indian J. Biochem. Biophys."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"G154","DOI":"10.1152\/ajpgi.00432.2006","article-title":"Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: The role of alpha5beta1-integrin","volume":"293","author":"Dodig","year":"2007","journal-title":"Am. J. Physiol. Gastrointest Liver Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1159\/000233252","article-title":"Fibronectin increases survival of rat hepatic stellate cells--a novel profibrogenic mechanism of fibronectin","volume":"24","year":"2009","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0168-8278(03)00161-2","article-title":"Initial signaling of the fibronectin receptor (alpha5beta1 integrin) in hepatic stellate cells is independent of tyrosine phosphorylation","volume":"39","author":"Milliano","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/j.1582-4934.2010.01072.x","article-title":"Integrin expression and function in the response of primary culture hepatic stellate cells to connective tissue growth factor (CCN2)","volume":"15","author":"Huang","year":"2011","journal-title":"J. Cell Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1073\/pnas.1017667108","article-title":"Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells","volume":"108","author":"Antonyak","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1089\/scd.2018.0200","article-title":"Exosomes Derived from Human Primed Mesenchymal Stem Cells Induce Mitosis and Potentiate Growth Factor Secretion","volume":"28","author":"Yuan","year":"2019","journal-title":"Stem Cells Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1039\/C7MB00146K","article-title":"Emergent properties of extracellular vesicles: A holistic approach to decode the complexity of intercellular communication networks","volume":"13","author":"Gho","year":"2017","journal-title":"Mol. Biosyst."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:30:28Z","timestamp":1760362228000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,25]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["cells9020290"],"URL":"https:\/\/doi.org\/10.3390\/cells9020290","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,25]]}}}