Hepatocyte transplantation is effective for treating liver failure, but healthy donors as a source of hepatocytes are quite limited.The livers of patients with hepatic fibrosis could be an alternative source; however, Work Shorts few reports have examined the nature of hepatocytes from fibrotic livers (f-hepatocytes).In this study, we compared the growth of f-hepatocytes and hepatocytes from normal livers (n-hepatocytes).Hepatocytes were isolated from normal and CCl 4 -treated wild-type Fischer rats that express dipeptidyl dipeptidase IV (DPPIV) gene (DPPIV + ).
The n- and f-hepatocytes proliferated in culture at similar rates.Both types of hepatocytes were transplanted into DPPIV - mutant Fischer rats that had been treated with retrorsine to injure the liver and were partially hepatectomized (PHx) before transplantation.Both n- and f-DPPIV + -hepatocytes proliferated and formed colonies.The colony sizes of f-hepatocytes 21 days posttransplantation were approximately three times those of n-hepatocytes.
The hepatocytes were analyzed using a fluorescence activated cell sorter (FACS).The FACS profile differed between f- and n-hepatocytes: f-hepatocytes were less granular, less autofluorescent, and smaller than n-hepatocytes.These characteristics of f-hepatocytes resembled those reported for Dog Toys small-sized n-hepatocytes (SHs), which are highly proliferative and preferentially express a unique set of 10 SH genes.However, f-hepatocytes preferentially expressed only five of the SH genes.
The expression profile of f-hepatocytes was rather similar to that of proliferating n-hepatocytes in the regenerating liver after PHx.The f-hepatocytes were morphologically normal and did not show any preneoplastic phenotype.These normal and proliferative natures of f-hepatocytes in vivo suggest the fibrotic liver as a source of hepatocytes for transplantation.