Fig. 6.

Repopulation of retrorsine-treated Nagase analbuminemic rat livers by donor hepatocytes. (a) Fourteen days after transplantation, donor cells from age-matched control, early cirrhotic, and advanced cirrhotic livers appeared to engraft with equal capacity bar = 150 µm. The albumin-expressing hepatocyte colonies were relatively small in size, as expected, and their numbers (b) were not significantly different among groups. (c) Early after transplantation, serum albumin levels in rats that received cells derived from donors with early cirrhosis and controls were significantly higher than in rats that received cells from cirrhotic rats with liver failure. The serum albumin levels in recipients with cell transplants from failing cirrhotic livers, however, recovered their capacity to expand and release albumin approximately 2 months after engraftment in noncir-rhotic livers. (d) Fourteen days after transplantation, there was a small difference in the percentage of the liver replaced by donor hepatocytes from control and early cirrhotic livers compared with that replaced by donor hepatocytes from failing cirrhotic livers (P < 0.05). (e) By posttransplantation day 42, there was considerable expansion of transplanted hepatocytes derived from controls and livers with early cirrhosis with coalescence of hepatocyte colonies, whereas expansion of transplanted hepatocytes recovered from failing cirrhotic livers was significantly less. By posttransplantation day 90, however, approximately 80% of the liver of all recipient rats was replaced by albumin-producing hepatocytes, independent of the source of the donor cells. Expression levels of previously measured liver-specific genes were assessed to determine whether recovered donor hepatocytes normalize function after transplantation. (f) qPCR demonstrated essentially no difference in ADH1a1, CYP4502b9, GST, FADS1, and transthyretin in the livers of repopulated animals irrespective of the source of donor cells used for transplantation.