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

Fotios Sampaziotis; Daniele Muraro; Olivia C. Tysoe; Stephen Sawiak; Timothy E. Beach; Edmund M. Godfrey; Sara S. Upponi; Teresa Brevini; Brandon T. Wesley; Jose Garcia-Bernardo; Krishnaa Mahbubani; Giovanni Canu; Richard Gieseck; Natalie L. Berntsen; Victoria L. Mulcahy; Keziah Crick; Corrina Fear; Sharayne Robinson; Lisa Swift; Laure Gambardella; Johannes Bargehr; Daniel Ortmann; Stephanie E. Brown; Anna Osnato; Michael P. Murphy; Gareth Corbett; William T. H. Gelson; George F. Mells; Peter Humphreys; Susan E. Davies; Irum Amin; Paul Gibbs; Sanjay Sinha; Sarah A. Teichmann; Andrew J. Butler; Teik Choon See; Espen Melum; Christopher J. E. Watson; Kourosh Saeb-Parsy; Ludovic Vallier

doi:10.1126/science.aaz6964

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

View ORCID ProfileFotios Sampaziotis¹,²,³,*,
View ORCID ProfileDaniele Muraro¹,
View ORCID ProfileOlivia C. Tysoe¹,⁴,
View ORCID ProfileStephen Sawiak⁵,
Timothy E. Beach⁴,
Edmund M. Godfrey⁶,
Sara S. Upponi⁶,
View ORCID ProfileTeresa Brevini¹,
View ORCID ProfileBrandon T. Wesley¹,
View ORCID ProfileJose Garcia-Bernardo⁷,
View ORCID ProfileKrishnaa Mahbubani⁴,
View ORCID ProfileGiovanni Canu¹,
Richard Gieseck III⁸,
View ORCID ProfileNatalie L. Berntsen⁹,¹⁰,¹¹,
View ORCID ProfileVictoria L. Mulcahy²,¹²,
Keziah Crick¹³,
Corrina Fear¹³,
View ORCID ProfileSharayne Robinson¹³,
View ORCID ProfileLisa Swift¹³,
View ORCID ProfileLaure Gambardella¹,²,
View ORCID ProfileJohannes Bargehr¹,²,¹⁴,
Daniel Ortmann¹,
Stephanie E. Brown¹,
View ORCID ProfileAnna Osnato¹,
View ORCID ProfileMichael P. Murphy¹⁵,
Gareth Corbett¹⁶,
William T. H. Gelson²,³,
George F. Mells²,³,¹²,
Peter Humphreys¹,
Susan E. Davies¹⁷,
Irum Amin⁴,¹³,
View ORCID ProfilePaul Gibbs⁴,¹³,
View ORCID ProfileSanjay Sinha ¹,²,
View ORCID ProfileSarah A. Teichmann⁷,¹⁸,
Andrew J. Butler⁴,¹³,
Teik Choon See⁶,
View ORCID ProfileEspen Melum⁹,¹⁰,¹¹,¹⁹,²⁰,
Christopher J. E. Watson⁴,¹³,²¹,²²,
View ORCID ProfileKourosh Saeb-Parsy⁴,¹³,†,
View ORCID ProfileLudovic Vallier¹,⁴,*,†

¹Wellcome–MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
²Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
³Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
⁴Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.
⁵Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK.
⁶Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
⁷Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.
⁸Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁹Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
¹⁰Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.
¹¹Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹²Academic Department of Medical Genetics, University of Cambridge, Cambridge, Cambridgeshire, UK.
¹³Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
¹⁴Division of Cardiovascular Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
¹⁵MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, Cambridgeshire, UK.
¹⁶Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
¹⁷Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
¹⁸Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, Cambridgeshire, UK.
¹⁹Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
²⁰Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
²¹National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU), Cambridge, Cambridgeshire, UK.
²²University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, Cambridgeshire, UK.

↵*Corresponding author. Email: fs347{at}cam.ac.uk (F.S.); lv225{at}cam.ac.uk (L.V.)

↵† These authors contributed equally to this work.

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Science 19 Feb 2021:
Vol. 371, Issue 6531, pp. 839-846
DOI: 10.1126/science.aaz6964

Fotios Sampaziotis

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

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

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

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For correspondence: fs347@cam.ac.uk lv225@cam.ac.uk

Daniele Muraro

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

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Olivia C. Tysoe

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

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

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Stephen Sawiak

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

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Timothy E. Beach

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

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Edmund M. Godfrey

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

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Sara S. Upponi

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

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Teresa Brevini

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

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Brandon T. Wesley

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

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Jose Garcia-Bernardo

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

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Krishnaa Mahbubani

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

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Giovanni Canu

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

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Richard Gieseck III

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

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Natalie L. Berntsen

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

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

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

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Victoria L. Mulcahy

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

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

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Keziah Crick

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

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Corrina Fear

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

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Sharayne Robinson

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

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Lisa Swift

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

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Laure Gambardella

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

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

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Johannes Bargehr

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

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

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

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Daniel Ortmann

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

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Stephanie E. Brown

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

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Anna Osnato

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

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Michael P. Murphy

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

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Gareth Corbett

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

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William T. H. Gelson

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

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

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George F. Mells

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

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

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

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Peter Humphreys

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

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Susan E. Davies

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

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Irum Amin

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

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

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Paul Gibbs

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

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

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Sanjay Sinha

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

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

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Sarah A. Teichmann

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

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

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Andrew J. Butler

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

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

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Teik Choon See

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

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Espen Melum

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

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

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

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

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

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Christopher J. E. Watson

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

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

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

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

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Kourosh Saeb-Parsy

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

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

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Ludovic Vallier

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

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

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For correspondence: fs347@cam.ac.uk lv225@cam.ac.uk

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

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