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Ectopic hepatocyte transplantation cures the pig model of tyrosinemia
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Academic Article
research paper
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Covid-on-the-Web dataset
has title
Ectopic hepatocyte transplantation cures the pig model of tyrosinemia
Creator
Han, Bing
Bansal, Aditya
Allen, Kari
Amiot, Bruce
Bhagwate, Aditya
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Source
BioRxiv
abstract
The effectiveness of cell-based therapies to treat liver failure is limited by the diseased liver environment. Herein we provide preclinical proof-of-concept for the treatment of liver failure through hepatocyte transplantation into lymph nodes in a large-animal model of hereditary tyrosinemia type 1 (HT1), a metabolic liver disease caused by deficiency of fumarylacetoacetate hydrolase (FAH) enzyme. FAH-deficient pigs received autologous hepatocyte transplantation into mesenteric lymph nodes after ex vivo transduction with a lentiviral vector carrying the pig Fah gene. Hepatocytes showed early (6 hour) and durable (8 month) engraftment in lymph nodes, with reproduction of vascular and hepatic microarchitecture. Subsequently, hepatocytes migrated to and repopulated the native diseased liver. The corrected cells generated enough liver mass to clinically ameliorate disease as early as 97 days post-transplantation, with complete normalization of tyrosine levels and liver function tests. Integration site analysis defined the corrected hepatocytes in the liver as a subpopulation of hepatocytes in the lymph nodes, indicating that the lymph nodes served as a source for healthy hepatocytes to repopulate a diseased liver. Ectopic transplantation of hepatocytes cures the pig model of HT1 and presents a promising approach to the treatment of liver disease in patients with pre-existing liver damage and fibrosis. One Sentence Summary Transplantation of corrected hepatocytes in mesenteric lymph nodes can cure fatal metabolic liver disease by providing organized liver tissue and by repopulating the diseased liver in the pig tyrosinemia model.
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2019-05-29
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10.1101/648493
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f3834d5a4af3161e1917825c5e5b5b4e610132a2
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https://doi.org/10.1101/648493
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Ectopic hepatocyte transplantation cures the pig model of tyrosinemia
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bioRxiv
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named entity 'tyrosinemia'
named entity 'hepatocytes'
named entity 'diseased liver'
named entity 'tyrosinemia'
named entity 'MESENTERIC LYMPH NODES'
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