{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:08:47Z","timestamp":1759226927256},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T00:00:00Z","timestamp":1509062400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T00:00:00Z","timestamp":1509062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{},{"award":["UO1AA018113"],"award-info":[{"award-number":["UO1AA018113"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>A patient with liver failure due to chronic and acute alcohol abuse under consideration for an urgent liver transplant shortly after stopping alcohol may have residual abnormalities that threaten transplant success, particularly for a small graft. To address this, we studied a model in which reduced\u2010size (50%) Lewis rat livers are transplanted into green fluorescence protein transgenic Lewis recipients after they are fed alcohol or a control diet for 5 weeks. Here we show that normal small Lewis grafts transplanted to alcohol\u2010fed Lewis hosts developed fibrosis, whereas no fibrosis was observed in control\u2010fed recipients. Host\u2010derived CD133\u2009+\u20098\u2010hydroxy\u20102\u2032\u2010deoxyguanosine (8\u2010OHdG) cells were significantly increased in livers recovered from both alcohol\u2010fed and control recipients, but only alcohol\u2010fed recipients demonstrated co\u2010staining (a marker of oxidative DNA damage). \u03b1 smooth muscle actin (\u03b1\u2010SMA) staining, a marker for myofibroblasts, also co\u2010localized with CD133\u2009+\u2009cells only in the livers of alcohol\u2010fed recipients. Immunostaining and polymerase chain reaction analysis confirmed that chronic alcohol consumption decreased the proportion of bone marrow stem cells (BMSCs) expressing CD133, c\u2010Kit, and chemokine (C\u2010X\u2010C motif) receptor 4 markers and caused oxidative mitochondria DNA (mtDNA) damage. Culture of CD133\u2009+\u2009cells from normal rats with medium containing 3% ethanol for 48 hours resulted in elevated mitochondrial 8\u2010OHdG and mtDNA deletion, and ethanol exposure diminished CD133 expression but dramatically increased \u03b1\u2010SMA expression. In conclusion, oxidative mtDNA damage and deletions occur in BMSCs of chronic alcohol\u2010fed recipients, and these damaged cells mobilize to the small liver grafts and become myofibroblasts where they play a key role in the subsequent development of fibrosis. <jats:italic toggle=\"yes\">Liver Transplantation 23 1564\u20131576 2017<\/jats:italic> AASLD.<\/jats:p>","DOI":"10.1002\/lt.24820","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T12:49:48Z","timestamp":1500382188000},"page":"1564-1576","source":"Crossref","is-referenced-by-count":2,"title":["Fibrosis in small syngeneic rat liver grafts because of damaged bone marrow stem cells from chronic alcohol consumption"],"prefix":"10.1097","volume":"23","author":[{"given":"Masayuki","family":"Hisada","sequence":"first","affiliation":[{"name":"Department of Surgery,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"Department of Surgery,Tokyo Medical University,Tokyo,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"Department of Pathology,Beijing Capital Medical University,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Surgery,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"Department of Surgery,Tokyo Medical University,Tokyo,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Surgery,Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Burdick","sequence":"additional","affiliation":[{"name":"Department of Surgery,Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George Melville","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Surgery,Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoli","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Surgery,Johns Hopkins University School of 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