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Stem cell\/induced pluripotent stem cell-derived exosomes have shown anti-senescence effects in various diseases. We applied novel organoid culture technology to establish and characterize cholangiocyte organoids (cholangioids) with oxidative stress-induced senescence and then investigated whether human placenta mesenchymal stem cell (hPMSC)-derived exosomes exerted a protective effect in senescent cholangioids.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We identified the growth characteristics of cholangioids by light microscopy and confocal microscopy. Exosomes were introduced concurrently with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> into the cholangioids. Using immunohistochemistry and immunofluorescence staining analyses, we assessed the expression patterns of the senescence markers p16<jats:sup>INK4a<\/jats:sup>, p21<jats:sup>WAF1\/Cip1<\/jats:sup>, and senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) and then characterized the mRNA and protein expression levels of chemokines and senescence-associated secretory phenotype (SASP) components.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Well-established cholangioids expressed cholangiocyte-specific markers. Oxidative stress-induced senescence enhanced the expression of the senescence-associated proteins p16<jats:sup>INK4a<\/jats:sup>, p21<jats:sup>WAF1\/Cip1<\/jats:sup>, and SA-\u03b2-gal in senescent cholangioids compared with the control group. Treatment with hPMSC-derived exosomes delayed the cholangioid aging progress and reduced the levels of SASP components (i.e., interleukin-6 and chemokine CC ligand 2).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Senescent organoids are a potential novel model for better understanding senescence progression in cholangiocytes. hPMSC-derived exosomes exert protective effects against senescent cholangioids under oxidative stress-induced injury by delaying aging and reducing SASP components, which might have therapeutic potential for PSC or PBC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-021-02271-3","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:03:27Z","timestamp":1616411007000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Human placenta mesenchymal stem cell-derived exosomes delay H2O2-induced aging in mouse cholangioids"],"prefix":"10.1186","volume":"12","author":[{"given":"Wenyi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-6867","authenticated-orcid":false,"given":"Hongcui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"2271_CR1","doi-asserted-by":"publisher","unstructured":"Campisi J, d\u2019Adda di Fagagna F. 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All protocols for human tissue and cell handling were approved by the Research Ethics Committee of the hospital (reference No. 2013-272).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"201"}}