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KMID : 0870420090130040189
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Korean Journal of Hepato-Biliary-Pancreatic Surgery
2009 Volume.13 No. 4 p.189 ~ p.197
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The Factors Affecting Transplanted Hepatocytes Repopulation in Rats with Liver Fibrosis
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Lee Sang-Woo
Min Seon-Ok
Choi Sae-Byeol
Kim Kyung-Sik
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Abstract
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Purpose: Cell therapy for various diseases has gained wide acceptance. Because most patients with chronic liver failure have mild-to-severe liver cirrhosis, there are many limitations to clinical applications. We analyzed how to increase cell engraftment in rats with liver fibrosis.
Methods: We used analbuminemic SD rats (NARs) as recipients of syngeneic CAG-EGFP SD hepatocytes obtained by the 2 perfusion method. Hepatic fibrosis was induced with thioacetamide in drinking water for 6 weeks in the recipient NARs. NARs were pre-treated with gadolinium, doxorubicin, and gliotoxin before hepatocyte transplantation. We evaluated the degree of cell engraftment by RT-PCR and immunofluorescent staining for GFP and albumin. The transplanted cells were detected by immunostaining for albumin, and serum albumin was also measured.
Results: Although detection of GFP by RT-PCR was variable, albumin was detected in all groups 4 wks after hepatocyte transplantation. GFP and albumin were also detected by immunofluorescent staining 1 and 4 wks after cell transplantation. In control rats, albumin production was maximal at 3 wks, and after that it rapidly decreased. In the gadolinium and doxorubicin-treated group, albumin production was increased up to 4 wks. Albumin production in the gadolinium-treated group was superior to that of the doxorubicin-treated group.
Conclusion: Kupffer cells play the most important role in cell engraftment in hepatic fibrosis. Therefore, perturbation of kupffer cells in hepatic fibrosis is needed to increase cell engraftment.
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KEYWORD
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Hepatocyte transplantation, Engraftment, Liver fibrosis, Kupffer cell, Analbuminemic rat (NAR)
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