{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:08:36Z","timestamp":1784693316001,"version":"3.55.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":58,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82160118, 82560134"],"award-info":[{"award-number":["82160118, 82560134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82404648 and 82260801"],"award-info":[{"award-number":["82404648 and 82260801"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Key Program of Guizhou Provincial Basic Research Program","award":["QKHJC-ZK [2025]-015"],"award-info":[{"award-number":["QKHJC-ZK [2025]-015"]}]},{"name":"the Project of Key Laboratory of Diagnosis and Treatment of Hepatobiliary and Pancreatic Diseases and Bioinformatics Research, Guizhou Medical University","award":["2024FY-001"],"award-info":[{"award-number":["2024FY-001"]}]},{"name":"Joint Medical Research Fund for High-Quality Development by the Guizhou Provincia Health Commission","award":["2024GZYXKYJJXM0050"],"award-info":[{"award-number":["2024GZYXKYJJXM0050"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"DOI":"10.1186\/s12951-026-04512-0","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:24:35Z","timestamp":1778675075000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MSC-derived apoptotic vesicles remodel hepatic macrophage polarization and suppress fibrosis via miR-6869-5p-mediated inhibition of FGF1 and HMGB1"],"prefix":"10.1186","volume":"24","author":[{"given":"Jin","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhuan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiqin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaxing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiliang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxue","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kegang","family":"Linghu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"issue":"Suppl 1","key":"4512_CR1","doi-asserted-by":"publisher","first-page":"S38","DOI":"10.1016\/S0168-8278(02)00429-4","volume":"38","author":"SL Friedman","year":"2003","unstructured":"Friedman SL. Liver fibrosis -- from bench to bedside. J Hepatol. 2003;38(Suppl 1):S38\u201353.","journal-title":"J Hepatol"},{"issue":"1","key":"4512_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.jhep.2018.09.014","volume":"70","author":"SK Asrani","year":"2019","unstructured":"Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol. 2019;70(1):151\u201371.","journal-title":"J Hepatol"},{"key":"4512_CR3","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-025-10835-1","author":"Y Xie","year":"2025","unstructured":"Xie Y, Zhang Z, Pan Y, Wang FS. Stem cells therapies for liver diseases: for current practice and future goals. Hepatol Int. 2025. https:\/\/doi.org\/10.1007\/s12072-025-10835-1.","journal-title":"Hepatol Int"},{"issue":"5","key":"4512_CR4","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41575-025-01050-2","volume":"22","author":"MC Ortu\u00f1o-Costela","year":"2025","unstructured":"Ortu\u00f1o-Costela MC, Pinzani M, Vallier L. Cell therapy for liver disorders: past, present and future. Nat Rev Gastroenterol Hepatol. 2025;22(5):329\u201342.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"6","key":"4512_CR5","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1007\/s12072-021-10199-2","volume":"15","author":"M Shi","year":"2021","unstructured":"Shi M, Li YY, Xu RN, Meng FP, Yu SJ, Fu JL, et al. Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial. Hepatol Int. 2021;15(6):1431\u201341.","journal-title":"Hepatol Int"},{"issue":"4","key":"4512_CR6","doi-asserted-by":"publisher","first-page":"389","DOI":"10.5966\/sctm.2014-0110","volume":"4","author":"JA Heslop","year":"2015","unstructured":"Heslop JA, Hammond TG, Santeramo I, Tort Piella A, Hopp I, Zhou J, et al. Concise review: workshop review: understanding and assessing the risks of stem cell-based therapies. Stem Cells Translational Medicine. 2015;4(4):389\u2013400.","journal-title":"Stem Cells Translational Medicine"},{"issue":"1","key":"4512_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02824-7","volume":"22","author":"Z Zhong","year":"2024","unstructured":"Zhong Z, Cui XL, Tan KJ, Wu XY, Zhu XJ, Zhang JY, et al. Apoptotic vesicles (apoVs) derived from fibroblast-converted hepatocyte-like cells effectively ameliorate liver fibrosis. J Nanobiotechnology. 2024;22(1):541.","journal-title":"J Nanobiotechnology"},{"key":"4512_CR8","doi-asserted-by":"publisher","first-page":"123510","DOI":"10.1016\/j.biomaterials.2025.123510","volume":"324","author":"H Zhang","year":"2025","unstructured":"Zhang H, Xing J, Sun M, Cui Y, Li Y, Hu S, et al. Engineered exosomes for targeted microRNA delivery to reverse liver fibrosis. Biomaterials. 2025;324:123510.","journal-title":"Biomaterials"},{"issue":"2","key":"4512_CR9","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1053\/j.gastro.2024.02.001","volume":"167","author":"B Sui","year":"2024","unstructured":"Sui B, Wang R, Chen C, Kou X, Wu D, Fu Y, et al. Apoptotic vesicular metabolism contributes to organelle assembly and safeguards liver homeostasis and regeneration. Gastroenterology. 2024;167(2):343\u201356.","journal-title":"Gastroenterology"},{"issue":"1","key":"4512_CR10","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s12951-023-01969-1","volume":"21","author":"L Yu","year":"2023","unstructured":"Yu L, Zhu G, Zhang Z, Yu Y, Zeng L, Xu Z, et al. Apoptotic bodies: bioactive treasure left behind by the dying cells with robust diagnostic and therapeutic application potentials. J Nanobiotechnology. 2023;21(1):218.","journal-title":"J Nanobiotechnology"},{"issue":"6","key":"4512_CR11","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1016\/j.jhep.2022.07.027","volume":"77","author":"V Brandel","year":"2022","unstructured":"Brandel V, Schimek V, G\u00f6ber S, Hammond T, Brunnthaler L, Schrottmaier WC, et al. Hepatectomy-induced apoptotic extracellular vesicles stimulate neutrophils to secrete regenerative growth factors. J Hepatol. 2022;77(6):1619\u201330.","journal-title":"J Hepatol"},{"issue":"10","key":"4512_CR12","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1016\/j.ymthe.2022.05.006","volume":"30","author":"Z Li","year":"2022","unstructured":"Li Z, Wu M, Liu S, Liu X, Huan Y, Ye Q, et al. Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration. Mol Ther. 2022;30(10):3193\u2013208.","journal-title":"Mol Ther"},{"issue":"1","key":"4512_CR13","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12951-024-02333-7","volume":"22","author":"Z Ding","year":"2024","unstructured":"Ding Z, Yan Z, Yuan X, Tian G, Wu J, Fu L, et al. Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity. J Nanobiotechnology. 2024;22(1):74.","journal-title":"J Nanobiotechnology"},{"key":"4512_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/biology11071059","author":"M New-Aaron","year":"2022","unstructured":"New-Aaron M, Dagur RS, Koganti SS, Ganesan M, Wang W, Makarov E, et al. Alcohol and HIV-derived hepatocyte apoptotic bodies induce hepatic stellate cell activation. Biology (Basel). 2022. https:\/\/doi.org\/10.3390\/biology11071059.","journal-title":"Biology (Basel)"},{"issue":"5","key":"4512_CR15","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1083\/jcb.201007162","volume":"193","author":"DG Wilson","year":"2011","unstructured":"Wilson DG, Phamluong K, Li L, Sun M, Cao TC, Liu PS, et al. Global defects in collagen secretion in a Mia3\/TANGO1 knockout mouse. J Cell Biol. 2011;193(5):935\u201351.","journal-title":"J Cell Biol"},{"issue":"3","key":"4512_CR16","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1002\/hep.28921","volume":"65","author":"JL Maiers","year":"2017","unstructured":"Maiers JL, Kostallari E, Mushref M, de Assuncao TM, Li H, Jalan-Sakrikar N, et al. The unfolded protein response mediates fibrogenesis and collagen I secretion through regulating TANGO1 in mice. Hepatology. 2017;65(3):983\u201398.","journal-title":"Hepatology"},{"issue":"9","key":"4512_CR17","doi-asserted-by":"publisher","first-page":"8646","DOI":"10.1021\/acsnano.3c01497","volume":"17","author":"Y You","year":"2023","unstructured":"You Y, Xu J, Liu Y, Li H, Xie L, Ma C, et al. Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke. ACS Nano. 2023;17(9):8646\u201362.","journal-title":"ACS Nano"},{"issue":"9","key":"4512_CR18","first-page":"2711","volume":"6","author":"S Jiang","year":"2021","unstructured":"Jiang S, Tian G, Yang Z, Gao X, Wang F, Li J, et al. Enhancement of acellular cartilage matrix scaffold by Wharton\u2019s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration. Bioact Mater. 2021;6(9):2711\u201328.","journal-title":"Bioact Mater"},{"key":"4512_CR19","first-page":"107","volume":"12","author":"L Xin","year":"2022","unstructured":"Xin L, Wei C, Tong X, Dai Y, Huang D, Chen J, et al. In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions. Bioact Mater. 2022;12:107\u201319.","journal-title":"Bioact Mater"},{"key":"4512_CR20","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.jconrel.2022.10.052","volume":"352","author":"Y Han","year":"2022","unstructured":"Han Y, Zhu Y, Youngblood HA, Almuntashiri S, Jones TW, Wang X, et al. Nebulization of extracellular vesicles: A promising small RNA delivery approach for lung diseases. J Control Release. 2022;352:556\u201369.","journal-title":"J Control Release"},{"issue":"7","key":"4512_CR21","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/s12276-022-00799-9","volume":"54","author":"L Hu","year":"2022","unstructured":"Hu L, Xie X, Xue H, Wang T, Panayi AC, Lin Z, et al. MiR-1224-5p modulates osteogenesis by coordinating osteoblast\/osteoclast differentiation via the Rap1 signaling target ADCY2. Exp Mol Med. 2022;54(7):961\u201372.","journal-title":"Exp Mol Med"},{"issue":"1\u20132","key":"4512_CR22","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s10495-024-02015-7","volume":"30","author":"X Li","year":"2025","unstructured":"Li X, Jiang Z, Li J, Yang K, He J, Deng Q, et al. PRELP inhibits colorectal cancer progression by suppressing epithelial-mesenchymal transition and angiogenesis via the inactivation of the FGF1\/PI3K\/AKT pathway. Apoptosis. 2025;30(1\u20132):16\u201334.","journal-title":"Apoptosis"},{"issue":"Pt 3","key":"4512_CR23","doi-asserted-by":"publisher","first-page":"118921","DOI":"10.1016\/j.jep.2024.118921","volume":"337","author":"P Shen","year":"2025","unstructured":"Shen P, Lin W, Huang Y, Ba X, Han L, Li T, et al. Wutou decoction attenuates rheumatoid arthritis in rats through SIRT1-mediated deacetylation of the HMGB1\/NF-\u03baB pathway. J Ethnopharmacol. 2025;337(Pt 3):118921.","journal-title":"J Ethnopharmacol"},{"key":"4512_CR24","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.reth.2024.01.003","volume":"25","author":"SP Chin","year":"2024","unstructured":"Chin SP, Marzuki M, Tai L, Mohamed Shahrehan NA, Ricky C, Fanty A, et al. Dynamic tracking of human umbilical cord mesenchymal stem cells (hUC-MSCs) following intravenous administration in mice model. Regen Ther. 2024;25:273\u201383.","journal-title":"Regen Ther"},{"issue":"1","key":"4512_CR25","doi-asserted-by":"publisher","first-page":"6495","DOI":"10.1038\/s41467-021-26834-3","volume":"12","author":"SHM Pang","year":"2021","unstructured":"Pang SHM, D\u2019Rozario J, Mendonca S, Bhuvan T, Payne NL, Zheng D, et al. Mesenchymal stromal cell apoptosis is required for their therapeutic function. Nat Commun. 2021;12(1):6495.","journal-title":"Nat Commun"},{"issue":"5","key":"4512_CR26","doi-asserted-by":"publisher","first-page":"e3001259","DOI":"10.1371\/journal.pbio.3001259","volume":"19","author":"SM Pontejo","year":"2021","unstructured":"Pontejo SM, Murphy PM. Chemokines act as phosphatidylserine-bound find-me signals in apoptotic cell clearance. PLoS Biol. 2021;19(5):e3001259.","journal-title":"PLoS Biol"},{"issue":"10","key":"4512_CR27","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1111\/liv.14940","volume":"41","author":"D Cheng","year":"2021","unstructured":"Cheng D, Chai J, Wang H, Fu L, Peng S, Ni X. Hepatic macrophages: key players in the development and progression of liver fibrosis. Liver Int. 2021;41(10):2279\u201394.","journal-title":"Liver Int"},{"issue":"1","key":"4512_CR28","volume":"19","author":"W Chen","year":"2024","unstructured":"Chen W, Lin F, Feng X, Yao Q, Yu Y, Gao F, et al. MSC-derived exosomes attenuate hepatic fibrosis in Primary Sclerosing Cholangitis through inhibition of Th17 differentiation. Asian J Pharm Sci. 2024;19(1):100889.","journal-title":"Asian J Pharm Sci"},{"key":"4512_CR29","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6696636","volume":"2021","author":"P Wang","year":"2021","unstructured":"Wang P, Ma Z, Wang Z, Wang X, Zhao G, Wang Z. MiR-6869-5p induces M2 polarization by regulating PTPRO in Gestational Diabetes Mellitus. Mediators Inflamm. 2021;2021:6696636.","journal-title":"Mediators Inflamm"},{"issue":"9","key":"4512_CR30","doi-asserted-by":"publisher","first-page":"6660","DOI":"10.1002\/jcp.26316","volume":"233","author":"S Yan","year":"2018","unstructured":"Yan S, Liu G, Jin C, Wang Z, Duan Q, Xu J, et al. MicroRNA-6869-5p acts as a tumor suppressor via targeting TLR4\/NF-\u03baB signaling pathway in colorectal cancer. J Cell Physiol. 2018;233(9):6660\u20138.","journal-title":"J Cell Physiol"},{"issue":"Pt A","key":"4512_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.120357","volume":"353","author":"X Fan","year":"2025","unstructured":"Fan X, Gao J, Liu S, Hua J, Shao D, Jia L, et al. Integration of network pharmacology and transcriptomics to reveal the mechanism of Paeoniae Radix Alba Polysaccharide in alleviating hepatic fibrosis. J Ethnopharmacol. 2025;353(Pt A):120357.","journal-title":"J Ethnopharmacol"},{"issue":"Pt 2","key":"4512_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.145580","volume":"319","author":"Y Qiu","year":"2025","unstructured":"Qiu Y, Bai X, Gao J, Tang B, Liu M, Ding J, et al. GalNAc-siRNA conjugates mediate the silencing of the parasite-derived lncRNA: A novel therapeutic approach for liver fluke-induced liver fibrosis. Int J Biol Macromol. 2025;319(Pt 2):145580.","journal-title":"Int J Biol Macromol"},{"issue":"4","key":"4512_CR33","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.tips.2024.02.006","volume":"45","author":"Z Erana-Perez","year":"2024","unstructured":"Erana-Perez Z, Igartua M, Santos-Vizcaino E, Hernandez RM. Genetically engineered loaded extracellular vesicles for drug delivery. Trends Pharmacol Sci. 2024;45(4):350\u201365.","journal-title":"Trends Pharmacol Sci"},{"issue":"1","key":"4512_CR34","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1186\/s12951-022-01636-x","volume":"20","author":"Y Lin","year":"2022","unstructured":"Lin Y, Yan M, Bai Z, Xie Y, Ren L, Wei J, et al. Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy. J Nanobiotechnology. 2022;20(1):432.","journal-title":"J Nanobiotechnology"},{"issue":"6","key":"4512_CR35","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70097","volume":"14","author":"M Auqui\u00e8re","year":"2025","unstructured":"Auqui\u00e8re M, Muccioli GG, des Rieux A. Methods and challenges in purifying drug-loaded extracellular vesicles. J Extracell Vesicles. 2025;14(6):e70097.","journal-title":"J Extracell Vesicles"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-026-04512-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-026-04512-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-026-04512-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:01:47Z","timestamp":1783695707000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12951-026-04512-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4512"],"URL":"https:\/\/doi.org\/10.1186\/s12951-026-04512-0","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"assertion":[{"value":"17 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with both the Declarations of Helsinki and Istanbul and was approved by the ethics committees of the research centers (Approval number: 2025\u2009\u2212\u2009177 and 2403022).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"636"}}