Brief Reports
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2005; 11(39): 6176-6181
Published online Oct 21, 2005. doi: 10.3748/wjg.v11.i39.6176
Quantitative evaluation of long-term liver repopulation and the reconstitution of bile ductules after hepatocellular transplantation
Yun-Wen Zheng, Nobuhiro Ohkohchi, Hideki Taniguchi
Yun-Wen Zheng, Hideki Taniguchi, Department of Regenerative Medicine, Graduate School of Medical Science, Yokohama City University, Yokohama 236-0004, Japan
Nobuhiro Ohkohchi, Yun-Wen Zheng, Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Hideki Taniguchi, Research Unit for Organ Regeneration, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan
Author contributions: All authors contributed equally to the work.
Supported by the National Project for Realization of ‘regenerative Medicine’ and Grants-in-Aid (14207046, 12557096) for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan and a grant from MITSUBISHI Foundation
Correspondence to: Professor Hideki Taniguchi, MD, PhD, Department of Regenerative Medicine, Graduate School of Medical Science, Yokohama City University, Fukuura 3-9, Kanazawa-Ku, Yokohama 236-0004, Japan. rtanigu@med.yokohama-cu.ac.jp
Telephone: +81-45-787-8963 Fax: +81-45-787-8963
Received: December 22, 2004
Revised: March 18, 2005
Accepted: March 21, 2005
Published online: October 21, 2005
Abstract

AIM: The treatment of liver disease is severely limited by a shortage of donor livers. In trying to address this growing problem, hepatocellular transplantation (HTx) has received much attention as an alternative to whole organ transplant. However, the expansion of transplanted cells is at low level, and the reconstitution of functional liver tissue is limited by this cellular property. We set up an animal model to better understand cell dose effect and the kinetics of liver repopulation following HTx.

METHODS: Dipeptidyl peptidase IV (DPPIV)-deficient rats treated with retrorsine and subjected to partial hepatectomy were infused with DPPIV-positive hepatocytes. Rats were injected with varying numbers of donor hepatocytes down to 100 cells low, and liver repopulation was examined at different time points up to 20 mo long. Repopulation was assessed by computer-aided quantitative detection.

RESULTS: Transplanted hepatocytes underwent multiple rounds of proliferation and stably repopulated the injured livers after 20 mo and at all cell doses. Transplanted cells divided 14 times within the 3-mo time period following infusion, and the liver repopulation reached a plateau between 3 and 20 mo. Approximately 90% replacement occurred. Donor-derived cells also reconstituted the bile ductules of the recipients.

CONCLUSION: The ability of transplanted hepatocytes to fully reconstitute injured livers strongly supports further investigation into the clinical potential of HTx. Additionally, the observation that transplanted hepatocytes also form components of the biliary system suggests that these cells may have bi-potential property of the stem cells.

Keywords: Hepatocellular transplantation; Hepatic stem cell; Kinetics; Cell dose; Long-term repopulation; Bile ductules; Quantification; In vivo; Therapeutic potential