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3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo
Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132688/ https://www.ncbi.nlm.nih.gov/pubmed/30155720 http://dx.doi.org/10.1007/s00204-018-2280-2 |
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author | Rashidi, Hassan Luu, Nguyet-Thin Alwahsh, Salamah M. Ginai, Maaria Alhaque, Sharmin Dong, Hua Tomaz, Rute A. Vernay, Bertrand Vigneswara, Vasanthy Hallett, John M. Chandrashekran, Anil Dhawan, Anil Vallier, Ludovic Bradley, Mark Callanan, Anthony Forbes, Stuart J. Newsome, Philip N. Hay, David C. |
author_facet | Rashidi, Hassan Luu, Nguyet-Thin Alwahsh, Salamah M. Ginai, Maaria Alhaque, Sharmin Dong, Hua Tomaz, Rute A. Vernay, Bertrand Vigneswara, Vasanthy Hallett, John M. Chandrashekran, Anil Dhawan, Anil Vallier, Ludovic Bradley, Mark Callanan, Anthony Forbes, Stuart J. Newsome, Philip N. Hay, David C. |
author_sort | Rashidi, Hassan |
collection | PubMed |
description | Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue lacking certain functions and long-term stability. Efforts to overcome these limiting factors have led to the building of three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application is limited due to their reliance on variable biological components. Our studies focused on the development of 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype for over 1 year in culture, providing an attractive resource for long-term in vitro studies. Moreover, 3D derived tissue provided critical liver support in two animal models, including immunocompetent recipients. Therefore, we believe that our study provides stable human tissue to better model liver biology ‘in the dish’, and in the future may permit the support of compromised liver function in humans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-018-2280-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6132688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-61326882018-09-13 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo Rashidi, Hassan Luu, Nguyet-Thin Alwahsh, Salamah M. Ginai, Maaria Alhaque, Sharmin Dong, Hua Tomaz, Rute A. Vernay, Bertrand Vigneswara, Vasanthy Hallett, John M. Chandrashekran, Anil Dhawan, Anil Vallier, Ludovic Bradley, Mark Callanan, Anthony Forbes, Stuart J. Newsome, Philip N. Hay, David C. Arch Toxicol In Vitro Systems Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue lacking certain functions and long-term stability. Efforts to overcome these limiting factors have led to the building of three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application is limited due to their reliance on variable biological components. Our studies focused on the development of 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype for over 1 year in culture, providing an attractive resource for long-term in vitro studies. Moreover, 3D derived tissue provided critical liver support in two animal models, including immunocompetent recipients. Therefore, we believe that our study provides stable human tissue to better model liver biology ‘in the dish’, and in the future may permit the support of compromised liver function in humans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-018-2280-2) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-08-28 2018 /pmc/articles/PMC6132688/ /pubmed/30155720 http://dx.doi.org/10.1007/s00204-018-2280-2 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | In Vitro Systems Rashidi, Hassan Luu, Nguyet-Thin Alwahsh, Salamah M. Ginai, Maaria Alhaque, Sharmin Dong, Hua Tomaz, Rute A. Vernay, Bertrand Vigneswara, Vasanthy Hallett, John M. Chandrashekran, Anil Dhawan, Anil Vallier, Ludovic Bradley, Mark Callanan, Anthony Forbes, Stuart J. Newsome, Philip N. Hay, David C. 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo |
title | 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo |
title_full | 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo |
title_fullStr | 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo |
title_full_unstemmed | 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo |
title_short | 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo |
title_sort | 3d human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo |
topic | In Vitro Systems |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132688/ https://www.ncbi.nlm.nih.gov/pubmed/30155720 http://dx.doi.org/10.1007/s00204-018-2280-2 |
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