Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice

Current cell-based treatment alternatives to organ transplantation for liver failure remain unsatisfactory. Hepatocytes have a strong tendency to dedifferentiate and apoptose when isolated and maintained in culture. In contrast, liver progenitor cells (LPCs) are robust, easy to culture and have been...

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Main Authors: Forster, N., Palmer, J., Yeoh, G., Ong, W., Mitchell, G., Slavin, J., Tirnitz-Parker, Janina, Morrison, W.
Format: Journal Article
Published: Mary Ann Liebert, Inc. Publishers 2011
Online Access:http://hdl.handle.net/20.500.11937/3349
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author Forster, N.
Palmer, J.
Yeoh, G.
Ong, W.
Mitchell, G.
Slavin, J.
Tirnitz-Parker, Janina
Morrison, W.
author_facet Forster, N.
Palmer, J.
Yeoh, G.
Ong, W.
Mitchell, G.
Slavin, J.
Tirnitz-Parker, Janina
Morrison, W.
author_sort Forster, N.
building Curtin Institutional Repository
collection Online Access
description Current cell-based treatment alternatives to organ transplantation for liver failure remain unsatisfactory. Hepatocytes have a strong tendency to dedifferentiate and apoptose when isolated and maintained in culture. In contrast, liver progenitor cells (LPCs) are robust, easy to culture and have been shown to replace damaged hepatocytes in liver disease. In this study we investigate whether isolated LPCs can survive and differentiate toward mature hepatocytes in vivo when implanted into a heterotopic mouse tissue engineering chamber model. Healthy Balb/c mice and those put on a choline-deficient ethionin-supplemented diet to induce chronic liver disease were implanted with a tissue engineering chamber based on the epigastric flow through pedicle model, containing either 1 × 106 LPCs suspended in Matrigel, or LPC-spheroids produced by preculture for 1 week in Matrigel. Four weeks after implantation the chamber contents were harvested. In all four groups, progenitor cells persisted in large numbers to 4 weeks and demonstrated evidence of considerable proliferation judged by Ki67-positive cells. Periodic acid Schiff staining demonstrated differentiation of some cells into mature hepatocytes. Constructs grown from LPC-spheroids demonstrated considerably greater LPC survival than those from LPCs that were grown as monolayers and implanted as dissociated cells. The combined use of LPC spheroids and the vascularized chamber model could be the basis for a viable alternative to current treatments for chronic liver failure.
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spelling curtin-20.500.11937-33492017-09-13T16:01:43Z Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice Forster, N. Palmer, J. Yeoh, G. Ong, W. Mitchell, G. Slavin, J. Tirnitz-Parker, Janina Morrison, W. Current cell-based treatment alternatives to organ transplantation for liver failure remain unsatisfactory. Hepatocytes have a strong tendency to dedifferentiate and apoptose when isolated and maintained in culture. In contrast, liver progenitor cells (LPCs) are robust, easy to culture and have been shown to replace damaged hepatocytes in liver disease. In this study we investigate whether isolated LPCs can survive and differentiate toward mature hepatocytes in vivo when implanted into a heterotopic mouse tissue engineering chamber model. Healthy Balb/c mice and those put on a choline-deficient ethionin-supplemented diet to induce chronic liver disease were implanted with a tissue engineering chamber based on the epigastric flow through pedicle model, containing either 1 × 106 LPCs suspended in Matrigel, or LPC-spheroids produced by preculture for 1 week in Matrigel. Four weeks after implantation the chamber contents were harvested. In all four groups, progenitor cells persisted in large numbers to 4 weeks and demonstrated evidence of considerable proliferation judged by Ki67-positive cells. Periodic acid Schiff staining demonstrated differentiation of some cells into mature hepatocytes. Constructs grown from LPC-spheroids demonstrated considerably greater LPC survival than those from LPCs that were grown as monolayers and implanted as dissociated cells. The combined use of LPC spheroids and the vascularized chamber model could be the basis for a viable alternative to current treatments for chronic liver failure. 2011 Journal Article http://hdl.handle.net/20.500.11937/3349 10.1089/ten.tec.2009.0519 Mary Ann Liebert, Inc. Publishers fulltext
spellingShingle Forster, N.
Palmer, J.
Yeoh, G.
Ong, W.
Mitchell, G.
Slavin, J.
Tirnitz-Parker, Janina
Morrison, W.
Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice
title Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice
title_full Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice
title_fullStr Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice
title_full_unstemmed Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice
title_short Expansion and Hepatocytic Differentiation of Liver Progenitor Cells In Vivo Using a Vascularized Tissue Engineering Chamber in Mice
title_sort expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice
url http://hdl.handle.net/20.500.11937/3349