A Pre-Clinical Large Animal Model of Sustained Liver Injury and Regeneration Stimulus View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Kenta Inomata, Kazuki Tajima, Hiroshi Yagi, Hisanobu Higashi, Hirofumi Shimoda, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Hanako Tsujikawa, Minoru Kitago, Masahiro Shinoda, Hideaki Obara, Osamu Itano, Alejandro Soto-Gutierrez, Yuko Kitagawa

ABSTRACT

A feasible large animal model to evaluate regenerative medicine techniques is vital for developing clinical applications. One such appropriate model could be to use retrorsine (RS) together with partial hepatectomy (PH). Here, we have developed the first porcine model using RS and PH. RS or saline control was administered intraperitoneally to Göttingen miniature pigs twice, two weeks apart. Four weeks after the second dose, animals underwent PH. Initially, we tested different doses of RS and resection of different amounts of liver, and selected 50 mg/kg RS with 60% hepatectomy as our model for further testing. Treated animals were sacrificed 3, 10, 17 or 28 days after PH. Blood samples and resected liver were collected. Serum and liver RS content was determined by Liquid Chromatograph-tandem Mass Spectrometer. Blood analyses demonstrated liver dysfunction after PH. Liver regeneration was significantly inhibited 10 and 17 days after PH in RS-treated animals, to the extent of 20%. Histological examination indicated hepatic injury and regenerative responses after PH. Immunohistochemical staining demonstrated accumulation of Cyclin D1 and suppression of Ki-67 and PCNA in RS-treated animals. We report the development of the first large animal model of sustained liver injury with suppression of hepatic regeneration. More... »

PAGES

14987

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-32889-y

DOI

http://dx.doi.org/10.1038/s41598-018-32889-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107377901

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30301901


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-32889-y'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-32889-y'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-32889-y'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-32889-y'


 

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