Correction of an inborn error of metabolism by intraportal hepatocyte transplantation in a dog model. 1996

J M Kocken, and I H Borel Rinkes, and A M Bijma, and W K de Roos, and E Bouwman, and O T Terpstra, and M Sinaasappel
Department of Pediatrics, University Hospital Rotterdam, The Netherlands.

The aims of this study were (1) to assess portal hemodynamics during intraportal hepatocyte transplantation (HTX) in dogs, (2) to evaluate a new method for the detection of transplanted hepatocytes using 5-bromo-2'-deoxyuridine (BrdU) incorporation, and (3) to determine the metabolic effects of HTX on an inborn error of the purine metabolism in dalmatian dogs. HTX was performed by intraportal infusion of freshly isolated allogeneic beagle hepatocytes. Portal flow and pressure were monitored continuously during HTX. For the detection experiments, beagles received hepatocytes that had been exposed to BrdU during regeneration of the donor liver, induced by partial hepatectomy. For metabolic studies, dalmatian dogs were used as recipients. Repetitive HTX was performed. As judged by the portal hemodynamics, the number of hepatocytes that could be infused safely varied from 5 x 1O(8) to 8 x 1O(8) in beagles, to 1 x 10(9) in dalmatians. Transaminase levels showed a 5- to 6-fold increase (P=0.05) after HTX, but normalized within 3 weeks. BrdU-positive cells were identified in the recipient livers 2 weeks after HTX and 5-10% of the total amount of transplanted hepatocytes was retrieved. A significant (P=0.05) decrease in serum uric acid was demonstrated after repeated HTX in dalmatians. In conclusion, (1) intraportal HTX is feasible, but portal hypertension limits the maximum amount of hepatocytes that can be infused in one HTX; (2) BrdU labeling is an attractive method for the detection of transplanted hepatocytes in the recipient liver; and (3) after two consecutive hepatocyte transplantations, a temporary correction of the purine metabolism was accomplished in the dalmatian dog.

UI MeSH Term Description Entries
D007432 Intraoperative Period The period during a surgical operation. Intraoperative Periods,Period, Intraoperative,Periods, Intraoperative
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008661 Metabolism, Inborn Errors Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero. Inborn Errors of Metabolism,Metabolism Errors, Inborn,Error, Inborn Metabolism,Errors Metabolism, Inborn,Errors Metabolisms, Inborn,Errors, Inborn Metabolism,Inborn Errors Metabolism,Inborn Errors Metabolisms,Inborn Metabolism Error,Inborn Metabolism Errors,Metabolism Error, Inborn,Metabolism Inborn Error,Metabolism Inborn Errors,Metabolisms, Inborn Errors
D011168 Portal System A system of vessels in which blood, after passing through one CAPILLARY BED, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. Portal Systems,System, Portal,Systems, Portal
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D012086 Reoperation A repeat operation for the same condition in the same patient due to disease progression or recurrence, or as followup to failed previous surgery. Revision, Joint,Revision, Surgical,Surgery, Repeat,Surgical Revision,Repeat Surgery,Revision Surgery,Joint Revision,Revision Surgeries,Surgery, Revision
D001973 Bromodeoxyuridine A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. BUdR,BrdU,Bromouracil Deoxyriboside,Broxuridine,5-Bromo-2'-deoxyuridine,5-Bromodeoxyuridine,NSC-38297,5 Bromo 2' deoxyuridine,5 Bromodeoxyuridine,Deoxyriboside, Bromouracil
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005240 Feasibility Studies Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. Feasibility Study,Studies, Feasibility,Study, Feasibility
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic

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