Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats.
OBJECTIVE
To investigate whether human hepatocytes could proliferate after transplantation to normal immunocompetent rats treated with 2-acetaminofluorene or retrorsine and partial hepatectomy.


METHODS
L02 hepatocyte-tolerant Sprague-Dawley rats were injected with retrorsine, 2-acetaminofluorene or normal saline. L02 hepatocytes were then transplanted via the spleen. Human albumin and its mRNA, specific proliferating cell nuclear antigen (PCNA), L02 hepatocyte dynamic distribution, number density and area density of PCNA-positive cells in the liver were determined.


RESULTS
All the examined indicators were not significantly different between the rats treated with 2-acetaminofluorene and normal saline, which was not the case with rats treated with retrorsine. A dynamic distribution of L02 hepatocytes in the rat liver was detected from wk 1 to mo 6 after transplantation in the retrorsine group and from wk 1 to 10 in the 2-acetaminofluorene group. Human albumin and its mRNA were detected from wk 2 to mo 6 in the retrorsine group and from wk 1 to 8 in the 2-acetaminofluorene group. Specific human PCNA was detected in the rat liver from wk 2 to mo 6 in the retrorsine group and from wk 2 to 6 in the 2-acetaminofluorene group. Human albumin and its mRNA contents as well as the number of PCNA positive cells reached a peak at wk 4.


CONCLUSIONS
L02 human hepatocytes could not proliferate significiantly after transplantation to the normal, immunocompetent rats treated with 2-acetaminofluorene. L02 human hepatocytes can survive for 10 wk after transplantation and express human albumin for 8 wk. L02 human hepatocytes can proliferate and express human albumin for 6 mo after transplantation to the rats treated with retrorsine. The chimeric L02 human hepatocytes, which then underwent transplantation into tolerant rats, were normal in morphogenesis, biochemistry and function.
Lin
Hu
H
Institute of Infectious Disease, Southwest Hospital, the Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, China.
Mao
Qing
Q
Wang
Yu-Ming
YM
Jiang
Li
L
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D002232:Carbocyanines; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D005260:Female; D005456:Fluorescent Dyes; D005865:Gestational Age; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007108:Immune Tolerance; D007121:Immunocompetence / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008115:Liver Regeneration / Q000187:drug effects; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D018183:Transplantation Chimera
D002232:Carbocyanines; D005456:Fluorescent Dyes; D018809:Proliferating Cell Nuclear Antigen; D011763:Pyrrolizidine Alkaloids; D012709:Serum Albumin; C024286:3,3'-dioctadecylindocarbocyanine; D015073:2-Acetylaminofluorene; C003300:retrorsine