Regional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation.

2.50
HDL Handle:
http://hdl.handle.net/10033/218411
Title:
Regional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation.
Authors:
Koenig, S; Yuan, Q; Krause, P; Christiansen, H; Rave-Fraenk, M; Kafert-Kasting, S; Kriegbaum, H; Schneider, A; Ott, M; Meyburg, J
Abstract:
Hepatocyte transplantation is regarded as a promising option to correct hereditary metabolic liver disease. This study describes a novel method involving regional transient portal ischemia (RTPI) in combination with hepatic irradiation (IR) as a preparative regimen for hepatocyte transplantation. The right lobules of rat livers (45% of liver mass) were subjected to RTPI of 30-120 min. Liver specimens and serum samples were analyzed for transaminase levels, DNA damage, apoptosis, and proliferation. Repopulation experiments involved livers of dipeptidylpeptidase IV (DPPIV)-deficient rats preconditioned with RTPI (60-90 min) either with or without prior partial hepatic IR (25 Gy). After reperfusion intervals of 1 and 24 h, 12 million wild-type (DPPIV positive) hepatocytes were transplanted into recipient livers via the spleen. RTPI of 60-90 min caused limited hepatic injury through necrosis and induced a distinct regenerative response in the host liver. Twelve weeks following transplantation, small clusters of donor hepatocytes were detected within the portal areas. Quantitative analysis revealed limited engraftment of 0.79% to 2.95%, whereas control animals (sham OP) exhibited 4.16% (determined as relative activity of DPPIV when compared to wild-type liver). Repopulation was significantly enhanced (21.43%) when IR was performed prior to RTPI, optimum preconditioning settings being 90 min of ischemia and 1 h of reperfusion before transplantation. We demonstrate that RTPI alone is disadvantageous to donor cell engraftment, whereas the combination of IR with RTPI comprises an effective preparative regimen for liver repopulation. The method described clearly has potential for clinical application.
Affiliation:
Department of General and Visceral Surgery, University Medical Centre Goettingen, Goettingen, Germany. skoenig1@gwdg.de
Citation:
Regional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation. 2011, 20 (2):303-11 Cell Transplant
Journal:
Cell transplantation
Issue Date:
2011
URI:
http://hdl.handle.net/10033/218411
DOI:
10.3727/096368910X520074
PubMed ID:
20719089
Type:
Article
Language:
en
ISSN:
1555-3892
Appears in Collections:
publications of AG Cell and Gene therapy

Full metadata record

DC FieldValueLanguage
dc.contributor.authorKoenig, Sen_GB
dc.contributor.authorYuan, Qen_GB
dc.contributor.authorKrause, Pen_GB
dc.contributor.authorChristiansen, Hen_GB
dc.contributor.authorRave-Fraenk, Men_GB
dc.contributor.authorKafert-Kasting, Sen_GB
dc.contributor.authorKriegbaum, Hen_GB
dc.contributor.authorSchneider, Aen_GB
dc.contributor.authorOtt, Men_GB
dc.contributor.authorMeyburg, Jen_GB
dc.date.accessioned2012-04-13T13:58:21Z-
dc.date.available2012-04-13T13:58:21Z-
dc.date.issued2011-
dc.identifier.citationRegional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation. 2011, 20 (2):303-11 Cell Transplanten_GB
dc.identifier.issn1555-3892-
dc.identifier.pmid20719089-
dc.identifier.doi10.3727/096368910X520074-
dc.identifier.urihttp://hdl.handle.net/10033/218411-
dc.description.abstractHepatocyte transplantation is regarded as a promising option to correct hereditary metabolic liver disease. This study describes a novel method involving regional transient portal ischemia (RTPI) in combination with hepatic irradiation (IR) as a preparative regimen for hepatocyte transplantation. The right lobules of rat livers (45% of liver mass) were subjected to RTPI of 30-120 min. Liver specimens and serum samples were analyzed for transaminase levels, DNA damage, apoptosis, and proliferation. Repopulation experiments involved livers of dipeptidylpeptidase IV (DPPIV)-deficient rats preconditioned with RTPI (60-90 min) either with or without prior partial hepatic IR (25 Gy). After reperfusion intervals of 1 and 24 h, 12 million wild-type (DPPIV positive) hepatocytes were transplanted into recipient livers via the spleen. RTPI of 60-90 min caused limited hepatic injury through necrosis and induced a distinct regenerative response in the host liver. Twelve weeks following transplantation, small clusters of donor hepatocytes were detected within the portal areas. Quantitative analysis revealed limited engraftment of 0.79% to 2.95%, whereas control animals (sham OP) exhibited 4.16% (determined as relative activity of DPPIV when compared to wild-type liver). Repopulation was significantly enhanced (21.43%) when IR was performed prior to RTPI, optimum preconditioning settings being 90 min of ischemia and 1 h of reperfusion before transplantation. We demonstrate that RTPI alone is disadvantageous to donor cell engraftment, whereas the combination of IR with RTPI comprises an effective preparative regimen for liver repopulation. The method described clearly has potential for clinical application.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Cell transplantationen_GB
dc.subject.meshAlanine Transaminaseen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAspartate Aminotransferasesen_GB
dc.subject.meshBiological Assayen_GB
dc.subject.meshHepatocytesen_GB
dc.subject.meshIschemiaen_GB
dc.subject.meshLiveren_GB
dc.subject.meshLiver Regenerationen_GB
dc.subject.meshLuminescenceen_GB
dc.subject.meshProliferating Cell Nuclear Antigenen_GB
dc.subject.meshRadiation, Ionizingen_GB
dc.subject.meshRatsen_GB
dc.subject.meshRats, Inbred F344en_GB
dc.subject.meshTime Factorsen_GB
dc.subject.meshTransplantation Conditioningen_GB
dc.titleRegional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation.en
dc.typeArticleen
dc.contributor.departmentDepartment of General and Visceral Surgery, University Medical Centre Goettingen, Goettingen, Germany. skoenig1@gwdg.deen_GB
dc.identifier.journalCell transplantationen_GB

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