期刊
GASTROENTEROLOGY
卷 140, 期 2, 页码 656-U402出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2010.11.006
关键词
Liver Transplantation; Liver Regeneration; Ectopic Organogenesis; Cell Therapies
资金
- Commonwealth of Pennsylvania
- National Institutes of Health [R01 DK085711]
BACKGROUND & AIMS: Hepatocyte transplantation is a potential therapeutic approach for liver disease. However, most patients with chronic hepatic damage have cirrhosis and fibrosis, which limit the potential for cell-based therapy of the liver. The development of an ectopic liver as an additional site of hepatic function represents a new approach for patients with end-stage liver disease. We investigated the development and function of liver tissue in lymph nodes in mice with liver failure. METHODS: Hepatocytes were isolated from 8- to 12-week-old mice and transplanted by intraperitoneal injection into 8- to 12-week-old fumarylacetoacetate hydrolase mice (Fah(-/-)), a model of the human liver disease tyrosinemia type I. Survival was monitored and the locations and functions of the engrafted liver cells were determined. RESULTS: Lymph nodes of Fah(-/-) mice were colonized by transplanted hepatocytes; Fah(+) hepatocytes were detected adjacent to the CD45(+) lymphoid cells of the lymphatic system. Ten weeks after transplantation, these mice had substantial improvements in serum levels of transaminases, bilirubin, and amino acids. Homeostatic expansion of donor hepatocytes in lymph nodes rescued the mice from lethal hepatic failure. CONCLUSIONS: Functional ectopic liver tissue in lymph nodes rescues mice from lethal hepatic disease; lymph nodes therefore might be used as sites for hepatocyte transplantation.
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