Abstract
Hepatocyte transplantation is an alternative to whole liver transplantation. Yet, the cellular and molecular mechansims prompting integration are largely unknown. We previously reported that the poor liver repopulation efficacy by transplanted hepatocytes in adult recipient livers is probably due to the host microenviroment and caused by the inefficient regulation of the growth hormon-IGF1-axis. The aim of this study was to investigate the effects of growth hormone on liver repopulation by transplantated hepatocytes. The age-dependent proliferative potential of wild type F344 rat hepatocytes was investigated after transplantation and administration of recombinant human growth hormon (rhGH) into old CD26-deficient F344 rat host livers. Repopulation rates were verified by flow cytometry and assay of CD26 enzyme activity. Cell cycle-dependent protein expression of C/EBPalpha and PP2A was determined. Detection of serum levels of rhGH indicated the efficient increase after systemic administration before and during hepatocyte transplantation. Hepatocytes isolated from either young or old donor rats formed bigger clusters of donor-derived hepatocytes in senescent host livers treated with rhGH as compared to untreated livers. Repopulation of senescent host livers by old or young hepatocytes after treatment with rhGH was 10 times higher as compared to untreated hosts. No functional difference between transplanted juvenile and senescent hepatocytes was observed in the host liver tissue as assessed by glycogen storage. The protein expression of C/EBPalpha and PP2A revealed the recovery of the senescent host liver microenviroment after treatment with rhGH favouring growth of transplanted hepatocytes, derived from both young and old donors, in the recipient senescent liver. Thus, in rats, the age of the recipient liver and the regulation along the growth hormone-IGF1-axis impacts repopulation by transplanted hepatocytes.
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