Quantitative evaluation of long-term liver repopulation and the reconstitution of bile ductules after hepatocellular transplantation.
OBJECTIVE
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.


CONCLUSIONS
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.
Zheng
Yun-Wen
YW
Department of Regenerative Medicine, Graduate School of Medical Science, Yokohama City University, Fukuura 3-9, Kanazawa-Ku, Yokohama 236-0004, Japan.
Ohkohchi
Nobuhiro
N
Taniguchi
Hideki
H
D000818:Animals; D001652:Bile Ducts / Q000166:cytology*; D002454:Cell Differentiation; D002455:Cell Division; D005260:Female; D006085:Graft Survival; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation*; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344