IngentaConnect Hepatic proliferation in Gunn rats transplanted with hepatocytes:...

Authors: Cubero, F. J.¹; Maganto, P.¹; Mula, N.¹; Ortiz, A.²; Barrutia, M. G.³; Codesal, F. J.⁴; Arahuetes, R. M.

Source: Cell Proliferation, Volume 38, Number 3, June 2005 , pp. 137-146(10)

Abstract:

Hepatocyte transplantation would offer an attractive alternative to liver transplantation in the treatment of inborn errors of liver metabolism. However, a major problem in most transplantation studies to date has been the limited growth of transplanted cells in the recipient organ. We performed a strategy for selective proliferation of transplanted cells by interfering with the proliferative capacity of resident hepatocytes, using the pyrrolizidine alkaloid retrorsine and then transplanting liver cells in conjunction with repeated administration of triiodothyronine, an inducer of hepatocyte proliferation in rats. In the present study, foetal and adult syngeneic hepatocyte transplantation into spleen was performed in retrorsine-treated hyperbilirubinemic Gunn rats. In parallel, repeated injections of triiodothyronine were given to recipients. Rats were sacrificed at 1, 7, 30 and 90 days after transplantation and blood and bile samples were taken to assess the functionality of transplanted cells. The proliferative activity of transplanted hepatocytes was evaluated using proliferating cell nuclear antigen labelling index. In summary, both adult and foetal hepatocyte transplantation were effective in correcting a metabolic abnormality in Gunn rats for as long as 3 months. The RS/T₃ model, as a measure to increase graft function, could represent an important advance to future clinical application of hepatocyte transplantation.

Document Type: Research article

DOI: 10.1111/j.1365-2184.2005.00338.x

Affiliations: 1: Servicio de Cirugía Experimental, Hospital Universitario Puerta de Hierro, Madrid, 2: Departamento de Fisiología, Facultad de Biología, Universidad Complutense, Madrid, 3: Departamento de Biología Celular, Facultad de Biología, Universidad Complutense, Madrid, and 4: Departamento de Morfología, Facultad de Medicina, Universidad Autónoma, Madrid

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Hepatic proliferation in Gunn rats transplanted with hepatocytes: effect of retrorsine and tri-iodothyronine