Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells
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Dahlke, Marc H; Loi, Roberto; Warren, Alessandra; Holz, Lauren; Popp, Felix C; Weiss, Daniel J; Piso, Pompiliu; Bowen, David G; McCaughan, Geoffrey W; Schlitt, Hans J; Bertolino, Patrick
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Background/Aims: 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...[Show more]
dc.contributor.author | Dahlke, Marc H | |
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dc.contributor.author | Loi, Roberto | |
dc.contributor.author | Warren, Alessandra | |
dc.contributor.author | Holz, Lauren | |
dc.contributor.author | Popp, Felix C | |
dc.contributor.author | Weiss, Daniel J | |
dc.contributor.author | Piso, Pompiliu | |
dc.contributor.author | Bowen, David G | |
dc.contributor.author | McCaughan, Geoffrey W | |
dc.contributor.author | Schlitt, Hans J | |
dc.contributor.author | Bertolino, Patrick | |
dc.date.accessioned | 2015-12-07T22:41:12Z | |
dc.identifier.issn | 0168-8278 | |
dc.identifier.uri | http://hdl.handle.net/1885/24206 | |
dc.description.abstract | Background/Aims: 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. | |
dc.publisher | Elsevier | |
dc.source | Journal of Hepatology | |
dc.subject | Keywords: major histocompatibility antigen; adoptive transfer; animal cell; animal experiment; animal model; antigen expression; article; bone marrow cell; cell function; cell fusion; cell infiltration; cell isolation; cell proliferation; controlled study; female; Bystander hepatitis; Cell therapy; Fusion; Stem cells; Transgenic T cells | |
dc.title | Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 44 | |
dc.date.issued | 2006 | |
local.identifier.absfor | 119999 - Medical and Health Sciences not elsewhere classified | |
local.identifier.ariespublication | u4020362xPUB31 | |
local.type.status | Published Version | |
local.contributor.affiliation | Dahlke, Marc H, University of Sydney | |
local.contributor.affiliation | Loi, Roberto, University of Vermont | |
local.contributor.affiliation | Warren, Alessandra , College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Holz, Lauren, University of Sydney | |
local.contributor.affiliation | Popp, Felix C, Universite Regensburg | |
local.contributor.affiliation | Weiss, Daniel J, University of Vermont | |
local.contributor.affiliation | Piso, Pompiliu, Universite Regensburg | |
local.contributor.affiliation | Bowen, David G, University of Sydney | |
local.contributor.affiliation | McCaughan, Geoffrey W, University of Sydney | |
local.contributor.affiliation | Schlitt, Hans J, Universite Regensburg | |
local.contributor.affiliation | Bertolino, Patrick, University of Sydney | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.startpage | 334 | |
local.bibliographicCitation.lastpage | 341 | |
local.identifier.doi | 10.1016/j.jhep.2005.07.023 | |
dc.date.updated | 2015-12-07T10:58:09Z | |
local.identifier.scopusID | 2-s2.0-30344473289 | |
Collections | ANU Research Publications |
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