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

Hassan Rashidi, Nguyet-Thin Luu, Salamah M Alwahsh, Maaria Ginai, Sharmin Alhaque, Hua Dong, Rute A Tomaz, Bertrand Vernay, Vasanthy Vigneswara, John M Hallett, Anil Chandrashekran, Anil Dhawan, Ludovic Vallier, Mark Bradley, Anthony Callanan, Stuart J Forbes, Philip N Newsome, David C Hay

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3117–3129
JournalArchives of toxicology
Volume92
Issue number10
Early online date28 Aug 2018
DOIs
Publication statusPublished - Oct 2018

Fingerprint Dive into the research topics of '3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo'. Together they form a unique fingerprint.

Cite this