Hepatocytes from fibrotic liver possess high growth potential in vivo.

Abstract

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, 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 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.

• Authors: Manabu Nishie, Chise Tateno, Rie Utoh, Toshihiko Kohashi, Norio Masumoto, Naoya Kobayashi, Toshiyuki Itamoto, Noriaki Tanaka, Toshimasa Asahara, Katsutoshi Yoshizato
• Journal: Cell transplantation (Cell Transplant) Vol. 18 Issue 5 Pg. 665-75 ( 2009) ISSN: 1555-3892 [Electronic] United States
• PMID: 19775529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Pyrrolizidine Alkaloids
• Dipeptidyl Peptidase 4
• retrorsine

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Proliferation
• Cell Transplantation (methods)
• Dipeptidyl Peptidase 4 (genetics, metabolism)
• Flow Cytometry
• Hepatectomy
• Hepatocytes (cytology, metabolism)
• Liver (cytology)
• Liver Cirrhosis (pathology)
• Liver Failure, Acute (chemically induced)
• Male
• Pyrrolizidine Alkaloids (pharmacology)
• Rats