Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA383149 | ENA |
REPOSITORIES: ENA
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Project description:Liver transplantation is the only therapeutic option for patients with end-stage liver disease. The shortage of donor organs has led to the search for alternative therapies to restore liver function and bridge patients to transplantation. Our previous work has shown that the proliferation of late gestation E19 fetal hepatocytes is mitogen-independent. This is manifested as differences in the control of ribosome biogenesis, global translation, cell cycle progression and gene expression. In the present study, we investigated whether E19 fetal hepatocytes would engraft and repopulate an injured adult liver. Methods: Fetal hepatocytes were isolated using a monoclonal antibody against a hepatic surface protein, leucine amino peptidase (LAP). LAP+ and LAP- fractions were analyzed by immunofluorescence and microarray. Immunopurified E19 liver cells from DPPIV+ F344 rats were transplanted via splenic injection into partial hepatectomized DPPIV- rats that had been pretreated with mitomycin C. Results: Phenotypic characterization of the LAP+ fetal hepatocytes revealed that more than a third of the isolated cells expressed ductal markers. Transcriptomic analysis revealed that these dual expressing cells represent a distinct subpopulation of less well differentiated hepatocytes. Transplanted immunopurified LAP+ late gestation fetal hepatocytes formed small hepatic, endothelial and occasional ductal colonies within one month. The average size of the colonies derived from the LAP+ cells increased so that by 10 months up to 35% of the liver was repopulated by donor-derived cells. Conclusions: Our studies show that late gestation fetal hepatocytes, despite their being far along in the differentiation process, possess the capacity for extensive liver repopulation. This is likely related to the unexpected presence of a significant proportion of hepatocyte marker-positive cells maintaining a less well differentiated phenotype.
2017-08-22 | GSE97897 | GEO
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