Cholangiocyte organoids can repair bile ducts after transplantation in the human liver-Reference-Cited by-同舟云学术

Cholangiocyte organoids can repair bile ducts after transplantation in the human liver

Published:2021-02-19 Issue:6531 Volume:371 Page:839-846
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Sampaziotis Fotios¹²³^ORCID,Muraro Daniele¹^ORCID,Tysoe Olivia C.¹⁴^ORCID,Sawiak Stephen⁵^ORCID,Beach Timothy E.⁴,Godfrey Edmund M.⁶,Upponi Sara S.⁶,Brevini Teresa¹^ORCID,Wesley Brandon T.¹^ORCID,Garcia-Bernardo Jose⁷^ORCID,Mahbubani Krishnaa⁴^ORCID,Canu Giovanni¹^ORCID,Gieseck Richard⁸,Berntsen Natalie L.⁹¹⁰¹¹^ORCID,Mulcahy Victoria L.²¹²^ORCID,Crick Keziah¹³,Fear Corrina¹³,Robinson Sharayne¹³^ORCID,Swift Lisa¹³^ORCID,Gambardella Laure¹²^ORCID,Bargehr Johannes¹²¹⁴^ORCID,Ortmann Daniel¹,Brown Stephanie E.¹,Osnato Anna¹^ORCID,Murphy Michael P.¹⁵^ORCID,Corbett Gareth¹⁶,Gelson William T. H.²³,Mells George F.²³¹²,Humphreys Peter¹,Davies Susan E.¹⁷,Amin Irum⁴¹³,Gibbs Paul⁴¹³^ORCID,Sinha Sanjay¹²^ORCID,Teichmann Sarah A.⁷¹⁸^ORCID,Butler Andrew J.⁴¹³,See Teik Choon⁶,Melum Espen⁹¹⁰¹¹¹⁹²⁰^ORCID,Watson Christopher J. E.⁴¹³²¹²²,Saeb-Parsy Kourosh⁴¹³^ORCID,Vallier Ludovic¹⁴^ORCID

Affiliation:

1. Wellcome–MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.

2. Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.

3. Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.

4. Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.

5. Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK.

6. Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.

7. Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.

8. Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

9. Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

10. Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.

11. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

12. Academic Department of Medical Genetics, University of Cambridge, Cambridge, Cambridgeshire, UK.

13. Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.

14. Division of Cardiovascular Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.

15. MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, Cambridgeshire, UK.

16. Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.

17. Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.

18. Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, Cambridgeshire, UK.

19. Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

20. Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

21. National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU), Cambridge, Cambridgeshire, UK.

22. University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, Cambridgeshire, UK.

Abstract

Organoids regenerate human bile ducts Bile ducts carry bile from the liver and gall bladder to the small intestine, where it aids digestion. Cholangiocytes are epithelial cells that line bile ducts and modify bile as its transported through the biliary tree. Chronic liver diseases involving cholangiocytes account for a large fraction of liver failure and the need for liver transplantation. Because liver donors are in short supply, Sampaziotis et al. used organoid technology to develop a cell-based therapy using human tissue (see the Perspective by Kurial and Willenbring). Cholangiocyte organoids were transplanted into the intrahepatic ducts of deceased human donor livers undergoing ex vivo normothermic perfusion. The livers could be maintained for up to 100 hours, and the transplanted organoids engrafted, exhibited function, and could repair bile ducts. Science , this issue p. 839 ; see also p. 786

Funder

Medical Research Council

National Institute for Health Research

British Heart Foundation

Academy of Medical Sciences

European Research Council

Rosetrees Trust

Addenbrooke's Charitable Trust, Cambridge University Hospitals

European Association for the Study of the Liver

Wellcome Trust Centre for Mitochondrial Research

Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre

Publisher