Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells
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. We have developed a transgenic mouse model of immune-mediated hepatitis to...
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| Veröffentlicht in: | Journal of hepatology 2006-02, Vol.44 (2), p.334-341 |
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| creator | 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 |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1016/j.jhep.2005.07.023 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/j.jhep.2005.07.023</identifier><identifier>PMID: 16225955</identifier><identifier>CODEN: JOHEEC</identifier><language>eng</language><publisher>Oxford: Elsevier B.V</publisher><subject>Animals ; Biological and medical sciences ; Bone Marrow Cells - cytology ; Bone Marrow Cells - immunology ; Bystander hepatitis ; Cell Communication - immunology ; Cell Fusion ; Cell therapy ; Disease Models, Animal ; Disease Progression ; Female ; Flow Cytometry ; Fusion ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatitis - immunology ; Hepatitis - pathology ; Hepatocytes - cytology ; Hepatocytes - immunology ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Mice ; Mice, Transgenic ; Other diseases. Semiology ; Stem cells ; T-Lymphocytes - immunology ; T-Lymphocytes - transplantation ; Transgenic T cells</subject><ispartof>Journal of hepatology, 2006-02, Vol.44 (2), p.334-341</ispartof><rights>2005 European Association for the Study of the Liver</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-b6b425d54f9bfdca6215c4c1b5110da71a438a772c9b3c71356180869adba9553</citedby><cites>FETCH-LOGICAL-c428t-b6b425d54f9bfdca6215c4c1b5110da71a438a772c9b3c71356180869adba9553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168827805004976$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17441849$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16225955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dahlke, Marc H.</creatorcontrib><creatorcontrib>Loi, Roberto</creatorcontrib><creatorcontrib>Warren, Alessandra</creatorcontrib><creatorcontrib>Holz, Lauren</creatorcontrib><creatorcontrib>Popp, Felix C.</creatorcontrib><creatorcontrib>Weiss, Daniel J.</creatorcontrib><creatorcontrib>Piso, Pompiliu</creatorcontrib><creatorcontrib>Bowen, David G.</creatorcontrib><creatorcontrib>McCaughan, Geoffrey W.</creatorcontrib><creatorcontrib>Schlitt, Hans J.</creatorcontrib><creatorcontrib>Bertolino, Patrick</creatorcontrib><title>Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>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.
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.
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.
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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - immunology</subject><subject>Bystander hepatitis</subject><subject>Cell Communication - immunology</subject><subject>Cell Fusion</subject><subject>Cell therapy</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fusion</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatitis - immunology</subject><subject>Hepatitis - pathology</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - immunology</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Other diseases. Semiology</subject><subject>Stem cells</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - transplantation</subject><subject>Transgenic T cells</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEuLFDEUhYMoTjv6B1xINrqrMknlVeBGBh8DA250HfK4hWmqKm2S6mb-_aTphtm5upvvHM79EHpPSU8JlZ_3_f4vHHpGiOiJ6gkbXqAdlYR0RHL6Eu0apDvNlL5Bb0rZE0IGMvLX6IZKxsQoxA7Z-2XZVugWCNFWCLg12hprLDjkeISC53TqZjjCjKetxLRiB_UEsF7I5B9rg-wasA3bXLFLK-DF5pxO2MM8l7fo1WTnAu-u9xb9-f7t993P7uHXj_u7rw-d50zXzknHmQiCT6ObgreSUeG5p05QSoJV1PJBW6WYH93gFR2EpJpoOdrgbHtluEWfLr2HnP5tUKpZYjkvsCukrRhFpBaDHhrILqDPqZQMkznk2BY_GkrMWazZm7NYcxZriDJNbAt9uLZvrrl6jlxNNuDjFbDF23nKdvWxPHOKc6r52LgvFw6ai2OEbIqPsPrmP4OvJqT4vx1PdWSXtg</recordid><startdate>20060201</startdate><enddate>20060201</enddate><creator>Dahlke, Marc H.</creator><creator>Loi, Roberto</creator><creator>Warren, Alessandra</creator><creator>Holz, Lauren</creator><creator>Popp, Felix C.</creator><creator>Weiss, Daniel J.</creator><creator>Piso, Pompiliu</creator><creator>Bowen, David G.</creator><creator>McCaughan, Geoffrey W.</creator><creator>Schlitt, Hans J.</creator><creator>Bertolino, Patrick</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20060201</creationdate><title>Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-b6b425d54f9bfdca6215c4c1b5110da71a438a772c9b3c71356180869adba9553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - cytology</topic><topic>Bone Marrow Cells - immunology</topic><topic>Bystander hepatitis</topic><topic>Cell Communication - immunology</topic><topic>Cell Fusion</topic><topic>Cell therapy</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fusion</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatitis - immunology</topic><topic>Hepatitis - pathology</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - immunology</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Other diseases. Semiology</topic><topic>Stem cells</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - transplantation</topic><topic>Transgenic T cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dahlke, Marc H.</creatorcontrib><creatorcontrib>Loi, Roberto</creatorcontrib><creatorcontrib>Warren, Alessandra</creatorcontrib><creatorcontrib>Holz, Lauren</creatorcontrib><creatorcontrib>Popp, Felix C.</creatorcontrib><creatorcontrib>Weiss, Daniel J.</creatorcontrib><creatorcontrib>Piso, Pompiliu</creatorcontrib><creatorcontrib>Bowen, David G.</creatorcontrib><creatorcontrib>McCaughan, Geoffrey W.</creatorcontrib><creatorcontrib>Schlitt, Hans J.</creatorcontrib><creatorcontrib>Bertolino, Patrick</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dahlke, Marc H.</au><au>Loi, Roberto</au><au>Warren, Alessandra</au><au>Holz, Lauren</au><au>Popp, Felix C.</au><au>Weiss, Daniel J.</au><au>Piso, Pompiliu</au><au>Bowen, David G.</au><au>McCaughan, Geoffrey W.</au><au>Schlitt, Hans J.</au><au>Bertolino, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>2006-02-01</date><risdate>2006</risdate><volume>44</volume><issue>2</issue><spage>334</spage><epage>341</epage><pages>334-341</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><coden>JOHEEC</coden><abstract>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.
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.
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.
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.</abstract><cop>Oxford</cop><pub>Elsevier B.V</pub><pmid>16225955</pmid><doi>10.1016/j.jhep.2005.07.023</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of hepatology, 2006-02, Vol.44 (2), p.334-341 |
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| subjects | Animals Biological and medical sciences Bone Marrow Cells - cytology Bone Marrow Cells - immunology Bystander hepatitis Cell Communication - immunology Cell Fusion Cell therapy Disease Models, Animal Disease Progression Female Flow Cytometry Fusion Gastroenterology. Liver. Pancreas. Abdomen Hepatitis - immunology Hepatitis - pathology Hepatocytes - cytology Hepatocytes - immunology Immunohistochemistry In Situ Hybridization, Fluorescence Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Mice Mice, Transgenic Other diseases. Semiology Stem cells T-Lymphocytes - immunology T-Lymphocytes - transplantation Transgenic T cells |
| title | Immune-mediated hepatitis drives low-level fusion between hepatocytes and adult bone marrow cells |
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