title: No evidence for recipient-derived hepatocytes in serial biopsies of sex-mismatched liver transplants.
abstract: BACKGROUND
  Bone marrow-derived hematopoietic stem cells (BM-HSCs) have been shown to act as source for hepatic regeneration in rodent models; however, their ability to participate in human liver regeneration remains controversial. The aim of this study was to investigate the origin of hepatocytes in sex-mismatched cases of orthotopic liver transplantation in longitudinally performed liver biopsies.
  
  
  METHODS
  Paraffin-embedded liver biopsy samples of 14 patients after sex-mismatched (female-to-male) liver transplantation were investigated. Biopsies were taken at multiple time points and subjected to histologic examination. Immunohistochemical staining with a hepatocyte-specific antibody and fluorescent in situ hybridization for visualization of Y chromosomes were performed to analyze the presence of recipient-derived hepatocytes.
  
  
  RESULTS
  We analyzed 30 liver biopsy samples ranging from 1 week to more than 3 years after transplantation. There was no evidence for recipient-derived hepatocytes in liver transplants at any time point. We were able to detect recipient-specific chromosomal status in inflammatory cells within the liver but not within hepatocytes. Results were independent of liver injury at the time of biopsy, caused by hepatitis C recurrence or rejection episodes.
  
  
  CONCLUSIONS
  Our results show no evidence for involvement of BM-HSCs in liver regeneration after orthotopic liver transplantation. We think that recipient BM-HSC-derived hepatocyte repopulation is a very rare event at best and is not of clinical relevance.
authors.affiliation: Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Pilat
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schoppmann
authors.forename: Judith
authors.initials: J
authors.lastname: Stift
authors.forename: Peter
authors.initials: P
authors.lastname: Mazal
authors.forename: Thomas
authors.initials: T
authors.lastname: Wekerle
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Berlakovich
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001854:Bone Marrow Cells / Q000473:pathology; D041322:Chromosomes, Human, Y; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000473:pathology*; D008115:Liver Regeneration; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012727:Sex Characteristics; D013997:Time Factors; D014180:Transplantation / Q000473:pathology*