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Influence of Stem Cell Mobilization and Liver Regeneration on Hepatic Parenchymal Chimerism in the Rat

Background. Despite the newly discovered plasticity of hematopoietic stem cells, their capacity to “transdifferentiate” into parenchymal cells and the regulation of this process is not yet elucidated. The present study was designed to investigate the effect of stem cell mobilization and liver regeneration on this process using a syngeneic rat female-to-male liver transplantation model. Methods. Rate and frequency of Y-chromosome containing hepatocytes was determined by fluorescence-in situ hybridization (FISH) using a rat Y-chromosome specific probe. Rats were subjected to full-size or partial liver transplantation with and without stem cell mobilization using granulocyte colony stimulating factor (G-CSF). The effect of stem cell mobilization was confirmed by assessing the white blood count and by evaluating the migration of granulopoietic precursor cells to the liver. Results. Treatment with G-CSF induced a twofold increase of peripheral white blood cells and a strong influx of granulopoietic precursor cells into the liver. Transplantation of a partial liver graft was followed by a 90% recovery of the original liver weight within a week, demonstrating the strong regenerative stimulus. Irrespective of the experimental model, the incidence and rate of Y-chromosome containing hepatocytes never exceeded 0.77%. Conclusion. Neither stem cell mobilization nor liver regeneration enhanced the incidence or rate of stem cell derived hepatocytes in a liver graft with unimpaired regenerative potential.