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- W2512079781 abstract "Introduction: Hepatocyte transplantation is regarded as a promising option to correct hereditary metabolic liver disease. This study describes a novel method involving transient and regional ischaemic damage in combination with external beam irradiation as a preparative regimen for hepatocyte transplantation. Methods: The right lobules of rat livers (45 % of liver mass) were subjected to transient regional portal ischaemia of 60–90 minutes. Liver specimens and serum samples were analysed for DNA damage, proliferation, and transaminase levels from 6h ours to up to 7d ays. Repopulation experiments involved livers of dipeptidylpeptidase IV (DPPIV) deficient rats preconditioned with ischaemia either with or without prior selective external beam irradiation (25 Gy). After reperfusion intervals of 1 hour and 24 hours, 12 million wild type (DPPIV + ) hepatocytes were transplanted into the recipient livers via the spleen. The degree of donor cell integration and growth was analysed 12 and 24 weeks after transplantation.Results: Regional ischaemia results in ischaemic liver damage as illustrated by highly elevated serum transaminase levels after 6 hours and a substantial proliferative response (PCNA-positive hepatocytes and BrdU incorporation) after 24 hours. Small clusters of donor hepatocytes were detected 24 weeks after transplantation. Quantitative analysis revealed the extent of repopulation to be 3.03 % and 3.12 % (1 and 24 hours reperfusion respectively), whereas control animals (sham OP) exhibited 9.85 % (determined as relative activity of DPPIV when compared to wild type liver). When liver irradiation was performed prior to selective ischaemia, repopulation exceeded 20 %. Conclusion: We demonstrate that regional portal liver ischaemia alone is disadvantageous to donor cell engraftment (with no major differences between reperfusion intervals of 1 and 24 hours), whereas the combination of ischaemia with irradiation comprises a suitable preparative regimen for liver repopulation. The method described has potential for viable clinical application." @default.
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- W2512079781 date "2009-01-01" @default.
- W2512079781 modified "2023-09-27" @default.
- W2512079781 title "Leberrepopulation nach konditionierendem Ischämie/ Reperfusionsschaden und partieller Leberbestrahlung Transient portal ischaemia and irradiation as preparative regimen for liver repopulation" @default.
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