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Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats.

ABSTRACT: AIM: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. CONCLUSION: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.

SUBMITTER: Lin H

PROVIDER: S-EPMC2705086 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats.

Lin Hu H Mao Qing Q Wang Yu-Ming YM Jiang Li L

World journal of gastroenterology 20080401 15

<h4>Aim</h4>To investigate whether human hepatocytes could proliferate after transplantation to normal immunocompetent rats treated with 2-acetaminofluorene or retrorsine and partial hepatectomy.<h4>Methods</h4>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, numb ...[more]

PMID: 18416458

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Project description:BackgroundThere is a huge controversy about whether xenograft or allograft in the "immune-privileged" brain needs immunosuppression. In animal studies, the prevailing sophisticated use of immunosuppression or immunodeficient animal is detrimental for the recipients, which results in a short lifespan of animals, confounds functional behavioral readout of the graft benefits, and discourages long-term follow-up.MethodsNeuron-restricted neural progenitor cells (NPCs) were derived from human embryonic stem cells (ESCs, including H1, its gene-modified cell lines for better visualization, and HN4), propagated for different passages, and then transplanted into the brain of immunocompetent rats without immunosuppressants. The graft survivals, their cell fates, and HLA expression levels were examined over time (up to 4 months after transplantation). We compared the survival capability of NPCs from different passages and in different transplantation sites (intra-parenchyma vs. para- and intra-cerebroventricle). The host responses to the grafts were also investigated.ResultsOur results show that human ESC-derived neuron-restricted NPCs survive extendedly in adult rat brain parenchyma with no need of immunosuppression whereas a late-onset graft rejection seems inevitable. Both donor HLA antigens and host MHC-II expression level remain relatively low with little change over time and cannot predict the late-onset rejection. The intra-/para-cerebroventricular human grafts are more vulnerable to the immune attack than the intrastriatal counterparts. Prevention of graft hyperplasia by using hypoproliferative late passaged human NPCs further significantly extends the graft survival time. Our new data also shows that a subpopulation of host microglia upregulate MHC-II expression in response to the human graft, but fail to present the human antigen to the host immune system, suggestive of the immune-isolation role of the blood-brain barrier (BBB).ConclusionsThe present study confirms the "immune privilege" of the brain parenchyma and, more importantly, unveils that choosing hypoproliferative NPCs for transplantation can benefit graft outcome in terms of both lower tumor-genic risk and the prolonged survival time without immunosuppression.

Dataset Information

Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats.

Publications

Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats.

Similar Datasets

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