{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:35:45Z","timestamp":1793424945982,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"DOI":"10.1186\/s13287-025-04743-2","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T12:34:50Z","timestamp":1762346090000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Stable production of immortalized hPC-MSC-derived extracellular vesicles: integrated cargo analysis and functional validation"],"prefix":"10.1186","volume":"16","author":[{"given":"Yingying","family":"Tong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuocheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"4743_CR1","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","volume":"30","author":"M Colombo","year":"2014","unstructured":"Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255\u201389. https:\/\/doi.org\/10.1146\/annurev-cellbio-101512-122326.","journal-title":"Annu Rev Cell Dev Biol"},{"key":"4743_CR2","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1083\/jcb.201211138","volume":"200","author":"G Raposo","year":"2013","unstructured":"Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373\u201383. https:\/\/doi.org\/10.1083\/jcb.201211138.","journal-title":"J Cell Biol"},{"key":"4743_CR3","doi-asserted-by":"publisher","unstructured":"Weng Z, et al. Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer. J Hematol Oncol. 2021Sep 3;14(1):136. https:\/\/doi.org\/10.1186\/s13045-021-01141-y","DOI":"10.1186\/s13045-021-01141-y"},{"issue":"3","key":"4743_CR4","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1084\/jem.183.3.1161","volume":"183","author":"G Raposo","year":"1996","unstructured":"Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183(3):1161\u201372. https:\/\/doi.org\/10.1084\/jem.183.3.1161.","journal-title":"J Exp Med"},{"key":"4743_CR5","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1111\/cas.12896","volume":"107","author":"Y Fujita","year":"2016","unstructured":"Fujita Y, Yoshioka Y, Ochiya T. Extracellular vesicle transfer of cancer pathogenic components. Cancer Sci. 2016;107:385\u201390. https:\/\/doi.org\/10.1111\/cas.12896.","journal-title":"Cancer Sci"},{"key":"4743_CR6","doi-asserted-by":"publisher","first-page":"18052","DOI":"10.1038\/s41598-017-18288-9","volume":"7","author":"TP Shentu","year":"2017","unstructured":"Shentu TP, et al. Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation. Sci Rep. 2017;7:18052. https:\/\/doi.org\/10.1038\/s41598-017-18288-9.","journal-title":"Sci Rep"},{"key":"4743_CR7","doi-asserted-by":"publisher","first-page":"170","DOI":"10.21037\/atm.2017.03.50","volume":"5","author":"L Beer","year":"2017","unstructured":"Beer L, Mildner M, Ankersmit HJ. Cell secretome based drug substances in regenerative medicine: when regulatory affairs Meet basic science. Ann Transl Med. 2017;5:170. https:\/\/doi.org\/10.21037\/atm.2017.03.50.","journal-title":"Ann Transl Med"},{"key":"4743_CR8","doi-asserted-by":"publisher","first-page":"816698","DOI":"10.3389\/fcell.2022.816698","volume":"10","author":"Y Zeng","year":"2022","unstructured":"Zeng Y, et al. Biological features of extracellular vesicles and challenges. Front Cell Dev Biol. 2022;10:816698. https:\/\/doi.org\/10.3389\/fcell.2022.816698.","journal-title":"Front Cell Dev Biol"},{"key":"4743_CR9","doi-asserted-by":"publisher","first-page":"114714","DOI":"10.1016\/j.bcp.2021.114714","volume":"192","author":"M Moloudizargari","year":"2021","unstructured":"Moloudizargari M, Asghari MH, Goel A. The therapeutic triad of extracellular vesicles: as drug targets, as drugs, and as drug carriers. Biochem Pharmacol. 2021;192:114714. https:\/\/doi.org\/10.1016\/j.bcp.2021.114714.","journal-title":"Biochem Pharmacol"},{"key":"4743_CR10","doi-asserted-by":"publisher","first-page":"e12162","DOI":"10.1002\/jev2.12162","volume":"11","author":"S Gelibter","year":"2022","unstructured":"Gelibter S, et al. The impact of storage on extracellular vesicles: A systematic study. J Extracell Vesicles. 2022;11:e12162. https:\/\/doi.org\/10.1002\/jev2.12162.","journal-title":"J Extracell Vesicles"},{"key":"4743_CR11","doi-asserted-by":"publisher","unstructured":"Azkargorta M, et al. Human serum extracellular vesicle proteomic profile depends on the enrichment method employed. Int J Mol Sci. 2021;22(20):11144. https:\/\/doi.org\/10.3390\/ijms222011144","DOI":"10.3390\/ijms222011144"},{"key":"4743_CR12","doi-asserted-by":"publisher","first-page":"113961","DOI":"10.1016\/j.addr.2021.113961","volume":"178","author":"D Gupta","year":"2021","unstructured":"Gupta D, Zickler AM, El Andaloussi S. Dosing extracellular vesicles. Adv Drug Deliv Rev. 2021;178:113961. https:\/\/doi.org\/10.1016\/j.addr.2021.113961.","journal-title":"Adv Drug Deliv Rev"},{"key":"4743_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/bios11120518","author":"MG Saad","year":"2021","unstructured":"Saad MG, Beyenal H, Dong WJ. Exosomes as powerful engines in cancer: Isolation, characterization and detection techniques. Biosens (Basel). 2021. https:\/\/doi.org\/10.3390\/bios11120518.","journal-title":"Biosens (Basel)"},{"key":"4743_CR14","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jconrel.2022.05.027","volume":"347","author":"I Kimiz-Gebologlu","year":"2022","unstructured":"Kimiz-Gebologlu I, Oncel SS, Exosomes. Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake. J Control Release. 2022;347:533\u201343. https:\/\/doi.org\/10.1016\/j.jconrel.2022.05.027.","journal-title":"J Control Release"},{"key":"4743_CR15","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s13287-020-01728-1","volume":"11","author":"Y Lin","year":"2020","unstructured":"Lin Y, Zhu W, Chen X. The involving progress of MSCs based therapy in atherosclerosis. Stem Cell Res Ther. 2020;11:216. https:\/\/doi.org\/10.1186\/s13287-020-01728-1.","journal-title":"Stem Cell Res Ther"},{"key":"4743_CR16","doi-asserted-by":"publisher","unstructured":"Li J, Ge Z, Ji W, Yuan N, Wang K. The proosteogenic and proangiogenic effects of small extracellular vesicles derived from bone marrow mesenchymal stem cells are attenuated in steroid-induced osteonecrosis of the femoral head. Biomed Res Int. 2020;2020:4176926. https:\/\/doi.org\/10.1155\/2020\/4176926","DOI":"10.1155\/2020\/4176926"},{"key":"4743_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-87371-3","author":"Y Tong","year":"2025","unstructured":"Tong Y, et al. A study on the production of extracellular vesicles derived from novel immortalized human placental mesenchymal stromal cells. Sci Rep. 2025. https:\/\/doi.org\/10.1038\/s41598-025-87371-3.","journal-title":"Sci Rep"},{"key":"4743_CR18","doi-asserted-by":"publisher","first-page":"100508","DOI":"10.1016\/j.repbio.2021.100508","volume":"21","author":"P Pethe","year":"2021","unstructured":"Pethe P, Kale V, Placenta. A gold mine for translational research and regenerative medicine. Reprod Biol. 2021;21:100508. https:\/\/doi.org\/10.1016\/j.repbio.2021.100508.","journal-title":"Reprod Biol"},{"key":"4743_CR19","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1126\/science.279.5349.349","volume":"279","author":"AG Bodnar","year":"1998","unstructured":"Bodnar AG, et al. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279:349\u201352. https:\/\/doi.org\/10.1126\/science.279.5349.349.","journal-title":"Science"},{"key":"4743_CR20","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0002-9440(10)63271-3","volume":"165","author":"RE Nisato","year":"2004","unstructured":"Nisato RE, et al. Generation and characterization of telomerase-transfected human lymphatic endothelial cells with an extended life span. Am J Pathol. 2004;165:11\u201324. https:\/\/doi.org\/10.1016\/S0002-9440(10)63271-3.","journal-title":"Am J Pathol"},{"key":"4743_CR21","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1002\/art.10116","volume":"46","author":"S Piera-Velazquez","year":"2002","unstructured":"Piera-Velazquez S, Jimenez SA, Stokes D. Increased life span of human Osteoarthritic chondrocytes by exogenous expression of telomerase. Arthritis Rheum. 2002;46:683\u201393. https:\/\/doi.org\/10.1002\/art.10116.","journal-title":"Arthritis Rheum"},{"key":"4743_CR22","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev.med.55.091902.103810","volume":"55","author":"VJ Thannickal","year":"2004","unstructured":"Thannickal VJ, Toews GB, White ES, Lynch JP, Martinez FJ. Mechanisms of pulmonary fibrosis. Annu Rev Med. 2004;55:395\u2013417. https:\/\/doi.org\/10.1146\/annurev.med.55.091902.103810.","journal-title":"Annu Rev Med"},{"key":"4743_CR23","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s00408-016-9912-1","volume":"194","author":"WA Wuyts","year":"2016","unstructured":"Wuyts WA, et al. First data on efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis and forced vital capacity of <\/=50 % of predicted value. Lung. 2016;194:739\u201343. https:\/\/doi.org\/10.1007\/s00408-016-9912-1.","journal-title":"Lung"},{"key":"4743_CR24","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1056\/NEJMoa1402582","volume":"370","author":"TE King Jr","year":"2014","unstructured":"King TE Jr., et al. A phase 3 trial of Pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083\u201392. https:\/\/doi.org\/10.1056\/NEJMoa1402582.","journal-title":"N Engl J Med"},{"key":"4743_CR25","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3906\/biy-1802-52","volume":"42","author":"Q He","year":"2018","unstructured":"He Q, Ye Z, Zhou Y, Tan WS. Comparative study of mesenchymal stem cells from rat bone marrow and adipose tissue. Turk J Biol. 2018;42:477\u201389. https:\/\/doi.org\/10.3906\/biy-1802-52.","journal-title":"Turk J Biol"},{"key":"4743_CR26","first-page":"75","volume":"7","author":"WS Khan","year":"2012","unstructured":"Khan WS, Hardingham TE. Mesenchymal stem cells, sources of cells and differentiation potential. J Stem Cells. 2012;7:75\u201385.","journal-title":"J Stem Cells"},{"key":"4743_CR27","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.jcyt.2019.08.002","volume":"21","author":"S Viswanathan","year":"2019","unstructured":"Viswanathan S, et al. Mesenchymal stem versus stromal cells: international society for cell & gene therapy (ISCT(R)) mesenchymal stromal cell committee position statement on nomenclature. Cytotherapy. 2019;21:1019\u201324. https:\/\/doi.org\/10.1016\/j.jcyt.2019.08.002.","journal-title":"Cytotherapy"},{"key":"4743_CR28","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1089\/scd.2014.0292","volume":"24","author":"Q Bai","year":"2015","unstructured":"Bai Q, et al. Temporal analysis of genome alterations induced by Single-Cell passaging in human embryonic stem cells. Stem Cells Dev. 2015;24:653\u201362. https:\/\/doi.org\/10.1089\/scd.2014.0292.","journal-title":"Stem Cells Dev"},{"key":"4743_CR29","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.1007\/s00216-015-8535-3","volume":"407","author":"VS Chernyshev","year":"2015","unstructured":"Chernyshev VS, et al. Size and shape characterization of hydrated and desiccated exosomes. Anal Bioanal Chem. 2015;407:3285\u2013301. https:\/\/doi.org\/10.1007\/s00216-015-8535-3.","journal-title":"Anal Bioanal Chem"},{"key":"4743_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16199-4","author":"O Saatci","year":"2020","unstructured":"Saatci O, et al. Targeting Lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Nat Commun. 2020;11(1):2416. https:\/\/doi.org\/10.1038\/s41467-020-16199-4","journal-title":"Nat Commun"},{"key":"4743_CR31","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.actbio.2021.07.009","volume":"131","author":"C Liu","year":"2021","unstructured":"Liu C, et al. Heterogeneous microenvironmental stiffness regulates pro-metastatic functions of breast cancer cells. Acta Biomater. 2021;131:326\u201340. https:\/\/doi.org\/10.1016\/j.actbio.2021.07.009.","journal-title":"Acta Biomater"},{"key":"4743_CR32","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1007\/s12015-017-9790-9","volume":"14","author":"L Tamo","year":"2018","unstructured":"Tamo L, et al. Gene network analysis of interstitial macrophages after treatment with induced pluripotent stem cells secretome (iPSC-cm) in the bleomycin injured rat lung. Stem Cell Rev Rep. 2018;14:412\u201324. https:\/\/doi.org\/10.1007\/s12015-017-9790-9.","journal-title":"Stem Cell Rev Rep"},{"key":"4743_CR33","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1046\/j.1365-2613.2002.00220.x","volume":"83","author":"G Izbicki","year":"2002","unstructured":"Izbicki G, Segel MJ, Christensen TG, Conner MW, Breuer R. Time course of bleomycin-induced lung fibrosis. Int J Exp Pathol. 2002;83:111\u20139. https:\/\/doi.org\/10.1046\/j.1365-2613.2002.00220.x.","journal-title":"Int J Exp Pathol"},{"key":"4743_CR34","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/imr.12614","volume":"281","author":"A Mantovani","year":"2018","unstructured":"Mantovani A, Barajon I, Garlanda C. IL-1 and IL-1 regulatory pathways in cancer progression and therapy. Immunol Rev. 2018;281:57\u201361. https:\/\/doi.org\/10.1111\/imr.12614.","journal-title":"Immunol Rev"},{"key":"4743_CR35","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.23812\/20-1-E","volume":"34","author":"P Conti","year":"2020","unstructured":"Conti P, et al. Coronavirus-19 (SARS-CoV-2) induces acute severe lung inflammation via IL-1 causing cytokine storm in COVID-19: a promising inhibitory strategy. J Biol Regul Homeost Agents. 2020;34:1971\u20135. https:\/\/doi.org\/10.23812\/20-1-E.","journal-title":"J Biol Regul Homeost Agents"},{"key":"4743_CR36","doi-asserted-by":"publisher","first-page":"692","DOI":"10.3389\/fimmu.2019.00692","volume":"10","author":"A Gabryelska","year":"2019","unstructured":"Gabryelska A, Kuna P, Antczak A, Bialasiewicz P, Panek M. IL-33 mediated inflammation in chronic respiratory Diseases-Understanding the role of the member of IL-1 superfamily. Front Immunol. 2019;10:692. https:\/\/doi.org\/10.3389\/fimmu.2019.00692.","journal-title":"Front Immunol"},{"key":"4743_CR37","doi-asserted-by":"publisher","first-page":"196","DOI":"10.3109\/08977194.2011.595714","volume":"29","author":"A Biernacka","year":"2011","unstructured":"Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-beta signaling in fibrosis. Growth Factors. 2011;29:196\u2013202. https:\/\/doi.org\/10.3109\/08977194.2011.595714.","journal-title":"Growth Factors"},{"key":"4743_CR38","doi-asserted-by":"publisher","first-page":"3675","DOI":"10.1172\/JCI94624","volume":"127","author":"Y Wei","year":"2017","unstructured":"Wei Y, et al. Fibroblast-specific Inhibition of TGF-beta1 signaling attenuates lung and tumor fibrosis. J Clin Invest. 2017;127:3675\u201388. https:\/\/doi.org\/10.1172\/JCI94624.","journal-title":"J Clin Invest"},{"key":"4743_CR39","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s10616-004-5123-3","volume":"45","author":"KM Lee","year":"2004","unstructured":"Lee KM, Choi KH, Ouellette MM. Use of exogenous hTERT to immortalize primary human cells. Cytotechnology. 2004;45:33\u20138. https:\/\/doi.org\/10.1007\/s10616-004-5123-3.","journal-title":"Cytotechnology"},{"key":"4743_CR40","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1042\/bj20120146","volume":"443","author":"T Sakuma","year":"2012","unstructured":"Sakuma T, Barry MA, Ikeda Y. Lentiviral vectors: basic to translational. Biochem J. 2012;443:603\u201318. https:\/\/doi.org\/10.1042\/bj20120146.","journal-title":"Biochem J"},{"key":"4743_CR41","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s12015-021-10290-z","volume":"18","author":"H Nam","year":"2022","unstructured":"Nam H, et al. Effects of Long-Term in vitro expansion on genetic stability and tumor formation capacity of stem cells. Stem Cell Rev Rep. 2022;18:241\u201357. https:\/\/doi.org\/10.1007\/s12015-021-10290-z.","journal-title":"Stem Cell Rev Rep"},{"key":"4743_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23","author":"T Liu","year":"2017","unstructured":"Liu T, Zhang L, Joo D, Sun S-C. NF-\u03baB signaling in inflammation. Signal Transduct Target Therapy. 2017. https:\/\/doi.org\/10.1038\/sigtrans.2017.23.","journal-title":"Signal Transduct Target Therapy"},{"key":"4743_CR43","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1158\/0008-5472.Can-24-0517","volume":"84","author":"M Akiyama","year":"2024","unstructured":"Akiyama M, et al. Nuclear factor-\u03baB p65 mediates tumor necrosis factor \u03b1-induced nuclear translocation of telomerase reverse transcriptase protein. Cancer Res. 2024;84:939\u2013939. https:\/\/doi.org\/10.1158\/0008-5472.Can-24-0517. Retraction.","journal-title":"Cancer Res"},{"key":"4743_CR44","doi-asserted-by":"publisher","unstructured":"Mei QR, Liu Z, Zuo H, Yang ZH, Qu J. Idiopathic pulmonary fibrosis: an update on pathogenesis. Front Pharmacol. 2022;12:797292. https:\/\/doi.org\/10.3389\/fphar.2021.797292","DOI":"10.3389\/fphar.2021.797292"},{"key":"4743_CR45","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","volume":"7","author":"C Th\u00e9ry","year":"2018","unstructured":"Th\u00e9ry C, et al. 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. J Extracell Vesicles. 2018;7:1535750. https:\/\/doi.org\/10.1080\/20013078.2018.1535750","journal-title":"J Extracell Vesicles"},{"key":"4743_CR46","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.128060","author":"N Mansouri","year":"2019","unstructured":"Mansouri N, et al. Mesenchymal stromal cell exosomes prevent and revert experimental pulmonary fibrosis through modulation of monocyte phenotypes. Jci Insight. 2019. https:\/\/doi.org\/10.1172\/jci.insight.128060.","journal-title":"Jci Insight"},{"key":"4743_CR47","doi-asserted-by":"publisher","first-page":"8613","DOI":"10.1002\/jcp.29706","volume":"235","author":"X Wan","year":"2020","unstructured":"Wan X, et al. Mesenchymal stem cell-derived extracellular vesicles suppress the fibroblast proliferation by downregulating FZD6 expression in fibroblasts via micrRNA-29b-3p in idiopathic pulmonary fibrosis. J Cell Physiol. 2020;235:8613\u201325. https:\/\/doi.org\/10.1002\/jcp.29706.","journal-title":"J Cell Physiol"},{"key":"4743_CR48","doi-asserted-by":"publisher","first-page":"4506303","DOI":"10.1155\/2019\/4506303","volume":"2019","author":"L Sun","year":"2019","unstructured":"Sun L, et al. Exosomal MiRNA Let-7 from menstrual Blood-Derived endometrial stem cells alleviates pulmonary fibrosis through regulating mitochondrial DNA damage. Oxid Med Cell Longev. 2019;2019: 4506303. https:\/\/doi.org\/10.1155\/2019\/4506303.","journal-title":"Oxid Med Cell Longev"},{"key":"4743_CR49","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo0987","author":"SY Gao","year":"2022","unstructured":"Gao SY, et al. PKM2 promotes pulmonary fibrosis by stabilizing TGF-\u03b21 receptor I and enhancing TGF-\u03b21 signaling. Sci Adv. 2022;8(38):eabo0987. https:\/\/doi.org\/10.1126\/sciadv.abo0987","journal-title":"Sci Adv"},{"key":"4743_CR50","doi-asserted-by":"publisher","first-page":"e12134","DOI":"10.1002\/jev2.12134","volume":"10","author":"MM Shi","year":"2021","unstructured":"Shi MM, et al. Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles. J Extracell Vesicles. 2021;10:e12134. https:\/\/doi.org\/10.1002\/jev2.12134.","journal-title":"J Extracell Vesicles"},{"key":"4743_CR51","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8091345","author":"J Guiot","year":"2019","unstructured":"Guiot J, et al. Exosomal MiRNAs in lung diseases: from biologic function to therapeutic targets. J Clin Med. 2019;8(9):1345. https:\/\/doi.org\/10.3390\/jcm8091345","journal-title":"J Clin Med"},{"key":"4743_CR52","doi-asserted-by":"publisher","first-page":"6917","DOI":"10.2147\/IJN.S264498","volume":"15","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, et al. A review of its Classification, isolation Techniques, Storage, diagnostic and targeted therapy applications. Int J Nanomed. 2020;15:6917\u201334. https:\/\/doi.org\/10.2147\/IJN.S264498. Exosome.","journal-title":"Int J Nanomed"},{"key":"4743_CR53","doi-asserted-by":"publisher","DOI":"10.14440\/jbm.2015.66","author":"MR Miller","year":"2015","unstructured":"Miller MR, Blystone SD. Reliable and inexpensive expression of large, tagged, exogenous proteins in murine bone marrow-derived macrophages using a second generation lentiviral system. J Biol Methods. 2015;2(3):e23. https:\/\/doi.org\/10.14440\/jbm.2015.66","journal-title":"J Biol Methods"},{"key":"4743_CR54","doi-asserted-by":"publisher","first-page":"7015","DOI":"10.7150\/thno.45359","volume":"10","author":"Y Zhao","year":"2020","unstructured":"Zhao Y, et al. Cortistatin protects against intervertebral disc degeneration through targeting mitochondrial ROS-dependent NLRP3 inflammasome activation. Theranostics. 2020;10:7015\u201333. https:\/\/doi.org\/10.7150\/thno.45359.","journal-title":"Theranostics"},{"key":"4743_CR55","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","volume":"34","author":"S Chen","year":"2018","unstructured":"Chen S, Zhou Y, Chen Y, Gu J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34:i884\u201390. https:\/\/doi.org\/10.1093\/bioinformatics\/bty560.","journal-title":"Bioinformatics"},{"key":"4743_CR56","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W. HTSeq\u2014a python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166\u20139. https:\/\/doi.org\/10.1093\/bioinformatics\/btu638.","journal-title":"Bioinformatics"},{"key":"4743_CR57","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12:357\u201360. https:\/\/doi.org\/10.1038\/nmeth.3317.","journal-title":"Nat Methods"},{"key":"4743_CR58","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated Estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8","journal-title":"Genome Biol"},{"key":"4743_CR59","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1007\/s00441-011-1215-5","volume":"347","author":"PR Baraniak","year":"2012","unstructured":"Baraniak PR, McDevitt TC. Scaffold-free culture of mesenchymal stem cell spheroids in suspension preserves multilineage potential. Cell Tissue Res. 2012;347:701\u201311. https:\/\/doi.org\/10.1007\/s00441-011-1215-5.","journal-title":"Cell Tissue Res"},{"key":"4743_CR60","doi-asserted-by":"publisher","first-page":"e0161915","DOI":"10.1371\/journal.pone.0161915","volume":"11","author":"Y Wang","year":"2016","unstructured":"Wang Y, et al. Spheroid formation of hepatocarcinoma cells in microwells: experiments and Monte Carlo simulations. PLoS ONE. 2016;11:e0161915. https:\/\/doi.org\/10.1371\/journal.pone.0161915.","journal-title":"PLoS ONE"},{"key":"4743_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-1825-3","author":"N Garcia-Romero","year":"2019","unstructured":"Garcia-Romero N, et al. Polyethylene glycol improves current methods for circulating extracellular vesicle-derived DNA isolation. J Transl Med. 2019;17(1):75. https:\/\/doi.org\/10.1186\/s12967-019-1825-3","journal-title":"J Transl Med"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04743-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04743-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04743-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T12:34:50Z","timestamp":1762346090000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04743-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4743"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04743-2","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]},"assertion":[{"value":"21 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Shanghai Telebio Biomedical Technology Co., Ltd., the source of the human cells used in this study, has confirmed that initial ethical approval was obtained for their collection and that informed consent was provided by all donors. The experimental animals used in this study were approved by the Animal Ethics Committee of Shanghai Institute of Pharmaceutical Industry Co., Ltd. The project titled \u201cCompound Treatment of Bleomycin-Induced Pulmonary Fibrosis in Rats\u201d with approval number A-2023-06-02 was granted on August 7, 2023.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We support inclusive, diverse, and equitable conduct of research.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Inclusion and diversity statement"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"619"}}