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

Archives of Toxicology
Hassan RashidiDavid C Hay

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...Continue Reading

References

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Citations

Oct 2, 2020·Biological Reviews of the Cambridge Philosophical Society·Ogechi OgokeNatesh Parashurama
Nov 23, 2019·Journal of Translational Medicine·Vahid HosseiniReza Rahbarghazi
Apr 3, 2020·Biological & Pharmaceutical Bulletin·Sayaka DeguchiHiroyuki Mizuguchi
Apr 9, 2020·Frontiers in Pharmacology·Daoyang FanZhongjun Liu
Sep 2, 2020·International Journal of Molecular Sciences·Cristina OlgasiAntonia Follenzi
Dec 24, 2018·Expert Opinion on Drug Metabolism & Toxicology·Wenli ZhouPierre Bagnaninchi
Aug 12, 2019·Archives of Toxicology·David Feuerborn
Nov 18, 2018·Archives of Toxicology·Patrick Nell
Jan 27, 2021·Stem Cell Research & Therapy·Meixian JinShuqin Zhou
Jan 5, 2021·Advanced Functional Materials·Dantong HuangKam W Leong
Feb 25, 2021·Nature Reviews. Materials·Moritz Hofer, Matthias P Lutolf
Mar 20, 2021·Veterinary Research·Camille BaquerreBertrand Pain
Apr 20, 2021·Basic & Clinical Pharmacology & Toxicology·Magnus Ingelman-Sundberg, Volker M Lauschke
Aug 12, 2021·Clinical and Translational Science·Kirk P Van NessEdward J Kelly
Dec 4, 2021·Frontiers in Bioengineering and Biotechnology·Wen-Ming LiuHe-Xin Yan

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Methods Mentioned

BETA
ELISA

Software Mentioned

Image
Pro Premier
Roche LightCycler 480

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