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Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model
Humanized liver rodent models, in which the host liver parenchyma is repopulated by human hepatocytes, have been increasingly used for drug development and disease research. Unlike the leading humanized liver mouse model in which Fumarylacetoacetate Hydrolase (Fah), Recombination Activating Gene (Ra...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388686/ https://www.ncbi.nlm.nih.gov/pubmed/35982097 http://dx.doi.org/10.1038/s41598-022-18119-6 |
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author | Carbonaro, Marisa Lee, Jeffrey Pefanis, Evangelos Desclaux, Mathieu Wang, Kehui Pennington, Alexander Huang, Hui Mujica, Alejo Rojas, Jose Ally, Roxanne Kennedy, Daniel Brown, Michael Rogulin, Vitaliy Moller-Tank, Sven Sabin, Leah Zambrowicz, Brian Thurston, Gavin Li, Zhe |
author_facet | Carbonaro, Marisa Lee, Jeffrey Pefanis, Evangelos Desclaux, Mathieu Wang, Kehui Pennington, Alexander Huang, Hui Mujica, Alejo Rojas, Jose Ally, Roxanne Kennedy, Daniel Brown, Michael Rogulin, Vitaliy Moller-Tank, Sven Sabin, Leah Zambrowicz, Brian Thurston, Gavin Li, Zhe |
author_sort | Carbonaro, Marisa |
collection | PubMed |
description | Humanized liver rodent models, in which the host liver parenchyma is repopulated by human hepatocytes, have been increasingly used for drug development and disease research. Unlike the leading humanized liver mouse model in which Fumarylacetoacetate Hydrolase (Fah), Recombination Activating Gene (Rag)-2 and Interleukin-2 Receptor Gamma (Il2rg) genes were inactivated simultaneously, generation of similar recipient rats has been challenging. Here, using Velocigene and 1-cell-embryo-targeting technologies, we generated a rat model deficient in Fah, Rag1/2 and Il2rg genes, similar to humanized liver mice. These rats were efficiently engrafted with Fah-expressing hepatocytes from rat, mouse and human. Humanized liver rats expressed human albumin and complement proteins in serum and showed a normal liver zonation pattern. Further, approaches were developed for gene delivery through viral transduction of human hepatocytes either in vivo, or in vitro prior to engraftment, providing a novel platform to study liver disease and hepatocyte-targeted therapies. |
format | Online Article Text |
id | pubmed-9388686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93886862022-08-20 Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model Carbonaro, Marisa Lee, Jeffrey Pefanis, Evangelos Desclaux, Mathieu Wang, Kehui Pennington, Alexander Huang, Hui Mujica, Alejo Rojas, Jose Ally, Roxanne Kennedy, Daniel Brown, Michael Rogulin, Vitaliy Moller-Tank, Sven Sabin, Leah Zambrowicz, Brian Thurston, Gavin Li, Zhe Sci Rep Article Humanized liver rodent models, in which the host liver parenchyma is repopulated by human hepatocytes, have been increasingly used for drug development and disease research. Unlike the leading humanized liver mouse model in which Fumarylacetoacetate Hydrolase (Fah), Recombination Activating Gene (Rag)-2 and Interleukin-2 Receptor Gamma (Il2rg) genes were inactivated simultaneously, generation of similar recipient rats has been challenging. Here, using Velocigene and 1-cell-embryo-targeting technologies, we generated a rat model deficient in Fah, Rag1/2 and Il2rg genes, similar to humanized liver mice. These rats were efficiently engrafted with Fah-expressing hepatocytes from rat, mouse and human. Humanized liver rats expressed human albumin and complement proteins in serum and showed a normal liver zonation pattern. Further, approaches were developed for gene delivery through viral transduction of human hepatocytes either in vivo, or in vitro prior to engraftment, providing a novel platform to study liver disease and hepatocyte-targeted therapies. Nature Publishing Group UK 2022-08-18 /pmc/articles/PMC9388686/ /pubmed/35982097 http://dx.doi.org/10.1038/s41598-022-18119-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Carbonaro, Marisa Lee, Jeffrey Pefanis, Evangelos Desclaux, Mathieu Wang, Kehui Pennington, Alexander Huang, Hui Mujica, Alejo Rojas, Jose Ally, Roxanne Kennedy, Daniel Brown, Michael Rogulin, Vitaliy Moller-Tank, Sven Sabin, Leah Zambrowicz, Brian Thurston, Gavin Li, Zhe Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model |
title | Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model |
title_full | Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model |
title_fullStr | Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model |
title_full_unstemmed | Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model |
title_short | Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model |
title_sort | efficient engraftment and viral transduction of human hepatocytes in an frg rat liver humanization model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388686/ https://www.ncbi.nlm.nih.gov/pubmed/35982097 http://dx.doi.org/10.1038/s41598-022-18119-6 |
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