title: Successful transplantation of reduced-sized rat alcoholic fatty livers made possible by mobilization of host stem cells.
abstract: Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for transplantation. Reduced sized (50%) livers or whole livers were transplanted into normal DA recipients, which, in this strain combination, survive indefinitely when the donor has not been fed alcohol. However, none of the rats survived a whole fatty liver transplant while six of seven recipients of reduced sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly increased in reduced size liver grafts compared to whole liver grafts. Lineage-negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the peripheral blood and in allografts after reduced size fatty liver transplantation. In contrast, there were meager increases in cells reactive with anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5 of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with neutralizing antibodies diminished stem cell recruitment and four of five reduced sized fatty liver recipients died. Thus chemokine insufficiency was associated with transplant failure of whole grafts, which was overcome by the increased regenerative requirements promoted by the small grafts and mediated by SDF-1 resulting in stem cell influx.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hisada
authors.forename: Y
authors.initials: Y
authors.lastname: Ota
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: A M
authors.initials: AM
authors.lastname: Cameron
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: R A
authors.initials: RA
authors.lastname: Montgomery
authors.forename: G M
authors.initials: GM
authors.lastname: Williams
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D001596:Benzylamines; D015153:Blotting, Western; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D000080027:Cyclams; D005235:Fatty Liver, Alcoholic / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D019650:Hematopoietic Stem Cell Mobilization; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016031:Liver Transplantation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; C088327:plerixafor