Transient portal ischaemia and irradiation as preparative regimen for liver repopulation
| Autor: | S. Kafert-Kasting, Hans Christiansen, Q. Yuan, Jochen Meyburg, Michael Ott, Margret Rave-Fränk, A. Schneider, H. Kriegbaum, Petra Krause, S. König |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
business.industry
DNA damage Ischemia Spleen 030230 surgery medicine.disease Transaminase Andrology Transplantation 03 medical and health sciences Liver disease 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis medicine business Dipeptidyl peptidase-4 Preparative Regimen |
| Zdroj: | Deutsche Gesellschaft für Chirurgie ISBN: 9783642006241 |
| DOI: | 10.1007/978-3-642-00625-8_62 |
| Popis: | 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 rightlobules 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 6 hours to up to 7 days. 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. |
| Databáze: | OpenAIRE |
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