Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells

Dahlke, Marc H. and Loi, Roberto and Warren, Alessandra and Holz, Lauren and Popp, Felix C. and Weiss, Daniel J. and Piso, Pompiliu and Bowen, David G. and McCaughan, Geoffrey W. and Schlitt, Hans J. and Bertolino, Patrick (2006) Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells. JOURNAL OF HEPATOLOGY, 44 (2). pp. 334-341. ISSN 0168-8278,

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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. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: HEMATOPOIETIC STEM-CELLS; MYELOMONOCYTIC CELLS; MACROPHAGE FUSION; IN-VIVO; LIVER; MICE; TRANSPLANTATION; REGENERATION; REPLACEMENT; ACTIVATION; fusion; cell therapy; bystander hepatitis; transgenic T cells; stem cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 24 Feb 2021 09:19
Last Modified: 24 Feb 2021 09:19
URI: https://pred.uni-regensburg.de/id/eprint/34999

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