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Characterization of long-term survival of syngeneic hepatocytes in rat peritoneum

Selden, C., Casbard, Angela, Themis, M. and Hodgson, H. J. 2003. Characterization of long-term survival of syngeneic hepatocytes in rat peritoneum. Cell Transplantation 12 (6) , pp. 569-578.

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Hepatocyte transplantation is a potential therapy for both acute and chronic hepatic insufficiency and also for treatment of inborn errors of metabolism affecting the liver. The peritoneum is one site for implantation and has several advantages: cells implanted there can be easily identified and observed, and it has a relatively large capacity. Long-term survival using "pure" hepatocytes in the peritoneum have been disappointing. We hypothesized that cotransplantation of hepatocytes with nonparenchymal cells would help maintain differentiated hepatocyte function. Rat liver cells transplanted intraperitoneally into August rats were sacrificed at 7 days, 1, 3, 6, 9, and 12 months and analyzed for presence, basal proliferation, and functionality of hepatocytes. To demonstrate that ectopic hepatocytes remained susceptible to exogenous growth factors affecting cell proliferation, rats 9 and 12 months after transplantation were stimulated with tri-iodothyronine and KGF. Hepatocytes were identified 7 days to >12 months, by H&E and immunohistochemically, as ectopic islands in the omental fat. Functionality was confirmed by glycogen deposition. Basal proliferation in 7-day rats was 28.0 +/- 10/1000 hepatocytes in ectopic islands (cf. 5.70 +/- 2.7/1000 in recipient liver). Proliferation in ectopic islands was greater than host liver. Growth factor-stimulated proliferation in ectopic islands induced a 70-fold increase in DNA synthesis. In conclusion, hepatocytes transplanted with nonparenchymal cells survive, proliferate, and function in the peritoneum of normal rats, and respond to exogenous growth stimuli. Their survival and proliferation in the presence of a normal functioning liver has implications for the potential use of the peritoneal site clinically for supplementation of liver function in metabolic disorders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Animals; cell differentiation/drug effects; cell differentiation/physiology; cell division/drug; effects; cell division/physiology; cell survival/drug effects; cell survival/physiology; cell transplantation/methods; cell transplantation/trends; cells; cultured; DNA/biosynthesis; female; glycogen/biosynthesis; graft survival/drug effects; graft survival/physiology; growth substances/pharmacology; hepatocytes/drug effects; hepatocytes/physiology; hepatocytes/transplantation; liver diseases/therapy; liver failure/therapy; male; peritoneum/cytology; peritoneum/physiology; peritoneum/surgery; rats; rats; inbred strains; rats; wistar; stromal cells/drug effects; stromal cells/physiology; stromal cells/transplantation; up-regulation/drug effects; up-regulation/physiology.
Publisher: Cognizant Communication Corporation
ISSN: 0963-6897
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Last Modified: 04 Jun 2017 06:27

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