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Organotypic liver culture in a fluid-air interface using slices of neonatal rat and adult human tissue - a model of fibrosis in vitro

Organotypic liver culture in a fluid-air interface using slices of neonatal rat and adult human tissue - a model of fibrosis in vitro
Organotypic liver culture in a fluid-air interface using slices of neonatal rat and adult human tissue - a model of fibrosis in vitro
Introduction: Fibrosis is the common end stage of most liver disease but there is no effective treatment currently available. We hypothesised that if viability of liver tissue slice culture could be improved, it should be possible to develop a model of liver fibrosis in vitro that could advance the development of antifibrotic therapy while at the same time reducing the need to use in vivo models. We have adapted a slice culture technique developed originally for organotypic culture of neural tissue to the liver.
Methods: slices of neonatal rat or adult human liver, 100–400-?m thick, were cut and cultured on nitrocellulose inserts at the air/fluid interface for up to 28 days.
Results: Hepatocytes expressed albumin by immunocytochemistry for up to 10 days and were viable for up to 21 days during which time new structures appeared, including cytokeratin 19 positive bile ductular structures and bands of smooth muscle actin positive stellate cells associated with new reticulin positive matrix. Smooth muscle actin expression by stellate cells could be pharmacologically inhibited by SDZ-RAD (everolimus).
Discussion: In conclusion, we have successfully developed a novel model of liver culture, which may prove useful in both studies of the mechanisms of liver fibrosis and in developing therapeutic strategies.
hepatic stellate cells, human, liver fibrosis, mouse, organotypic method, rat, slice culture
1056-8719
103-110
Verrill, Clare
aebaa0d4-fb62-4bf6-97ab-5f9bb23cf9a3
Davies, Janice
8aace1be-5b4c-4c72-be07-5867f09e39be
Millward-Sadler, Harry
db60d76b-22ce-4da2-85b7-40ddd5734378
Sundstrom, Lars
6d63d054-c735-4fcd-9cfc-2d41d68a06eb
Sheron, Nick
cbf852e3-cfaa-43b2-ab99-a954d96069f1
Verrill, Clare
aebaa0d4-fb62-4bf6-97ab-5f9bb23cf9a3
Davies, Janice
8aace1be-5b4c-4c72-be07-5867f09e39be
Millward-Sadler, Harry
db60d76b-22ce-4da2-85b7-40ddd5734378
Sundstrom, Lars
6d63d054-c735-4fcd-9cfc-2d41d68a06eb
Sheron, Nick
cbf852e3-cfaa-43b2-ab99-a954d96069f1

Verrill, Clare, Davies, Janice, Millward-Sadler, Harry, Sundstrom, Lars and Sheron, Nick (2002) Organotypic liver culture in a fluid-air interface using slices of neonatal rat and adult human tissue - a model of fibrosis in vitro. Journal of Pharmacological and Toxicological Methods, 48 (2), 103-110. (doi:10.1016/S1056-8719(03)00042-X).

Record type: Article

Abstract

Introduction: Fibrosis is the common end stage of most liver disease but there is no effective treatment currently available. We hypothesised that if viability of liver tissue slice culture could be improved, it should be possible to develop a model of liver fibrosis in vitro that could advance the development of antifibrotic therapy while at the same time reducing the need to use in vivo models. We have adapted a slice culture technique developed originally for organotypic culture of neural tissue to the liver.
Methods: slices of neonatal rat or adult human liver, 100–400-?m thick, were cut and cultured on nitrocellulose inserts at the air/fluid interface for up to 28 days.
Results: Hepatocytes expressed albumin by immunocytochemistry for up to 10 days and were viable for up to 21 days during which time new structures appeared, including cytokeratin 19 positive bile ductular structures and bands of smooth muscle actin positive stellate cells associated with new reticulin positive matrix. Smooth muscle actin expression by stellate cells could be pharmacologically inhibited by SDZ-RAD (everolimus).
Discussion: In conclusion, we have successfully developed a novel model of liver culture, which may prove useful in both studies of the mechanisms of liver fibrosis and in developing therapeutic strategies.

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More information

Published date: 2002
Keywords: hepatic stellate cells, human, liver fibrosis, mouse, organotypic method, rat, slice culture

Identifiers

Local EPrints ID: 27463
URI: http://eprints.soton.ac.uk/id/eprint/27463
ISSN: 1056-8719
PURE UUID: b4af7e9d-7645-42fc-b31a-de310379c30d
ORCID for Nick Sheron: ORCID iD orcid.org/0000-0001-5232-8292

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Date deposited: 28 Apr 2006
Last modified: 15 Mar 2024 07:18

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Contributors

Author: Clare Verrill
Author: Janice Davies
Author: Harry Millward-Sadler
Author: Lars Sundstrom
Author: Nick Sheron ORCID iD

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