title: Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells.
abstract: OBJECTIVE
  The role of adult bone marrow-derived cells (BMC) in hepatic regeneration is controversial. Both transdifferentiation of BMC as well as fusion with hepatocytes have been suggested in toxin-based and genetic selection models.
  
  
  METHODS
  We have developed a transgenic mouse model of immune-mediated hepatitis to clarify the role of BMC in liver regeneration following injury mediated by T cells.
  
  
  RESULTS
  Repeated adoptive transfer of transgenic T cells into bone marrow chimeras resulted in multiple waves of hepatitis. Hepatocytes derived from donor bone marrow were identified using a self-protein that does not interfere with hepatocyte function and proliferation in recipient animals. Some cells contained one recipient nucleus and another independent donor bone marrow-derived nucleus, suggesting that cellular fusion plays some role in liver repair after immune hepatitis. However, despite pronounced infiltration by myeloid cells, the frequency of fusion was extremely low.
  
  
  CONCLUSIONS
  This study provides a unique, clinically relevant model in which fusion hepatocytes can be purified and characterized by the expression of donor MHC antigen. It demonstrates that although fusion between BMC and hepatocytes occurs under conditions of inflammation that correspond to human disease, its frequency needs to be increased to be of any therapeutic value.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, Sydney, Australia. mhdahlke@web.de
authors.forename: Marc H
authors.initials: MH
authors.lastname: Dahlke
authors.forename: Roberto
authors.initials: R
authors.lastname: Loi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Warren
authors.forename: Lauren
authors.initials: L
authors.lastname: Holz
authors.forename: Felix C
authors.initials: FC
authors.lastname: Popp
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.forename: Pompiliu
authors.initials: P
authors.lastname: Piso
authors.forename: David G
authors.initials: DG
authors.lastname: Bowen
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: Patrick
authors.initials: P
authors.lastname: Bertolino
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002459:Cell Fusion; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation