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3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo

Rashidi, H; Luu, N-T; Alwahsh, SM; Ginai, M; Alhaque, S; Dong, H; Tomaz, RA; ... Hay, DC; + view all (2018) 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo. Archives of Toxicology , 92 (10) pp. 3117-3129. 10.1007/s00204-018-2280-2. Green open access

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Abstract

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.

Type: Article
Title: 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00204-018-2280-2
Publisher version: http://doi.org/10.1007/s00204-018-2280-2
Language: English
Additional information: Copyright information © The Author(s) 2018 Open Access This 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.
Keywords: Liver tissue, Pluripotent stem cell, Stable cell phenotype, Implantable liver graft, Interdisciplinary research
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10056373
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