Korean J Hepatobiliary Pancreat Surg.
2009 Dec;13(4):189-197.
The Factors Affecting Transplanted Hepatocytes Repopulation in Rats with Liver Fibrosis
- Affiliations
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- 1Department of Surgery, Yonsei University College of Medicine, Korea. kskim88@yuhs.ac
- 2Graduate Program of Nano Science and Technology, Graduate School of Yonsei University, Korea.
- 3Department of Surgery, Korea University College of Medicine, Korea.
- 4Cell Therapy Center, Severance Hospital, Yonsei University College of Medicine, Korea.
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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