title: Bone marrow stem cells contribute to alcohol liver fibrosis in humans.
abstract: Bone marrow-derived stem cell (BMSC) contribution to liver repair varies considerably and recent evidence suggests these cells may contribute to liver fibrosis. We investigated the mobilization and hepatic recruitment of bone marrow (BM) stem cells in patients with alcohol liver injury and their contribution to parenchymal/non-parenchymal liver cell lineages. Liver biopsies from alcoholic hepatitis (AH) patients and male patients, who received a female liver transplant and developed AH, were analyzed for BM stem cell content by fluorescence in situ hybridization and immunostaining. Y chromosome analysis was performed, along with co-staining for hepatocyte, biliary, myofibroblast, and Ki-67 markers. Blood CD34(+) levels were quantified in AH patients by flow cytometry. AH patients had increased CD34(+) cell counts in liver tissue (1.834% +/- 0.605%; P < 0.05) and in blood (0.195% +/- 0.063%; P < 0.05) as compared with matched controls (0.299% + 0.208% and 0.067% +/- 0.01%). A proportion of hepatic myofibroblasts were BM-derived (7.9%-26.8%) as deemed by the co-localization of Y chromosome/alpha-smooth muscle actin (alpha-SMA) staining. In the cross-sex liver grafts with AH, 5.025% of the myofibroblasts were co-staining for CD34, suggesting that a population of CD34(+) cells were contributing to the hepatic myofibroblast population. There was no evidence of BM contribution to hepatocyte or biliary cell differentiation, nor evidence of increased hepatocyte regeneration. Alcohol liver injury mobilizes CD34(+) stem cells into the circulation and recruits them into the liver. These BMSCs contribute to the hepatic myofibroblast population but not to parenchymal lineages and do not promote hepatocyte repair.
authors.affiliation: Department of Hepatology, University of Edinburgh, Edinburgh, UK. e.dalakas@ed.ac.uk
authors.forename: Evangelos
authors.initials: E
authors.lastname: Dalakas
authors.forename: Philip N
authors.initials: PN
authors.lastname: Newsome
authors.forename: Shelagh
authors.initials: S
authors.lastname: Boyle
authors.forename: Rachael
authors.initials: R
authors.lastname: Brown
authors.forename: Anne
authors.initials: A
authors.lastname: Pryde
authors.forename: Shonna
authors.initials: S
authors.lastname: McCall
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: John N
authors.initials: JN
authors.lastname: Plevris
mesh_terms: D000199:Actins / Q000097:blood / Q000378:metabolism; D000328:Adult; D018952:Antigens, CD34 / Q000097:blood / Q000378:metabolism; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D016031:Liver Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism; D012737:Sex Factors; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1