Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells.
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.
Dahlke
Marc H
MH
Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, Sydney, Australia. mhdahlke@web.de
Loi
Roberto
R
Warren
Alessandra
A
Holz
Lauren
L
Popp
Felix C
FC
Weiss
Daniel J
DJ
Piso
Pompiliu
P
Bowen
David G
DG
McCaughan
Geoffrey W
GW
Schlitt
Hans J
HJ
Bertolino
Patrick
P
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