About: Ectopic hepatocyte transplantation cures the pig model of tyrosinemia

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Ectopic hepatocyte transplantation cures the pig model of tyrosinemia
Creator	Han, Bing Bansal, Aditya Allen, Kari Amiot, Bruce Bhagwate, Aditya Cheikhi, Amin Degrado, Timothy Du, Zeji Francipane, Maria Garg, Ishan Guthman, Rebekah Hickey, Raymond Jiang, Huailei Kaiser, Robert Kocher, Jean-Pierre Lagasse, Eric Lillegard, Joseph Lowe, Val Nicolas, Clara Nyberg, Scott O'brien, Daniel Pandey, Mukesh Suksanpaisan, Lukkana Sw, St Vanlith, Caitlin
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.
has issue date	2019-05-29(xsd:dateTime)
bibo:doi	10.1101/648493
has license	biorxiv
sha1sum (hex)	f3834d5a4af3161e1917825c5e5b5b4e610132a2
schema:url	https://doi.org/10.1101/648493
resource representing a document's title	Ectopic hepatocyte transplantation cures the pig model of tyrosinemia
schema:publication	bioRxiv
resource representing a document's body	covid:f3834d5a4af3161e1917825c5e5b5b4e610132a2#body_text
is schema:about of	named entity 'tyrosinemia' named entity 'hepatocytes' named entity 'diseased liver' named entity 'tyrosinemia' named entity 'MESENTERIC LYMPH NODES' named entity 'PROVIDING' named entity 'METABOLIC LIVER DISEASE' named entity 'pig' named entity 'mesenteric lymph nodes' named entity 'liver tissue' named entity 'liver diseases' named entity 'Hereditary tyrosinemia type 1' named entity 'histology' named entity 'organ systems' named entity 'liver' named entity 'bioinformatics' named entity 'liver failure' named entity 'ammonia' named entity 'NTBC' named entity 'NIS' named entity 'cirrhosis' named entity 'fibrosis' named entity 'liver' named entity 'liver' named entity 'clinically relevant' named entity 'lymph node' named entity 'clinical setting' named entity 'vector' named entity 'hepatocyte' named entity 'heat map' named entity 'hepatocytes' named entity 'introns' named entity 'mesenteric lymph nodes' named entity 'NADH dehydrogenase' named entity 'lymph nodes' named entity 'reporter gene' named entity 'transcription start sites' named entity 'GraphPad Prism' named entity 'Hepatocyte' named entity 'liver' named entity 'flavoprotein' named entity 'hepatocytes' named entity 'lymph node' named entity 'percutaneous' named entity 'hepatocytes' named entity '14,000' named entity 'ligase' named entity 'non-invasive' named entity 'liver' named entity 'allele' named entity 'hepatocytes' named entity 'lymph nodes' named entity 'lymph nodes' named entity 'lymph node' named entity 'acute liver failure' named entity 'bps' named entity 'nucleotides' named entity 'transcription factors' named entity 'exogenously' named entity 'liver injury'

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