Intrahepatic transplantation of normal hepatocytes prevents Wilson's disease in Long-Evans cinnamon rats

Gastroenterology
Y YoshidaK Ogawa

Abstract

Long-Evans cinnamon (LEC) rats are an animal model of Wilson's disease. This study investigated whether intrahepatic transplantation of normal hepatocytes can prevent Wilson's disease in LEC rats. Hepatocytes of newborn Long-Evans agouti (LEA) rats were transplanted into the livers of LEC rats before onset of hepatic disease. Expression of normal transcripts from the gene linked to Wilson's disease was investigated at 30 weeks of age by reverse-transcription polymerase chain reaction and in situ hybridization. Eight of 16 (50.0%) untreated LEC rats died of hepatic failure during 20-30 weeks of age. Of the 27 LEC rats with transplanted cells, 2 (7.4%) died of hepatic failure and 4 died of ileus complicated by the surgical treatment. In the recipient livers, the transplanted cells comprised 4%-20% of the hepatocyte populations, expressing normal messenger RNA transcribed from the Wilson's disease gene, and hepatic copper deposition was reduced to approximately 60% of that in untreated LEC rats. Transplantation of normal hepatocytes prevents Wilson's disease in LEC rats.

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