Your browser doesn't support javascript.
loading
Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.
Sampaziotis, Fotios; Muraro, Daniele; Tysoe, Olivia C; Sawiak, Stephen; Beach, Timothy E; Godfrey, Edmund M; Upponi, Sara S; Brevini, Teresa; Wesley, Brandon T; Garcia-Bernardo, Jose; Mahbubani, Krishnaa; Canu, Giovanni; Gieseck, Richard; Berntsen, Natalie L; Mulcahy, Victoria L; Crick, Keziah; Fear, Corrina; Robinson, Sharayne; Swift, Lisa; Gambardella, Laure; Bargehr, Johannes; Ortmann, Daniel; Brown, Stephanie E; Osnato, Anna; Murphy, Michael P; Corbett, Gareth; Gelson, William T H; Mells, George F; Humphreys, Peter; Davies, Susan E; Amin, Irum; Gibbs, Paul; Sinha, Sanjay; Teichmann, Sarah A; Butler, Andrew J; See, Teik Choon; Melum, Espen; Watson, Christopher J E; Saeb-Parsy, Kourosh; Vallier, Ludovic.
Afiliação
  • Sampaziotis F; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK. fs347@cam.ac.uk lv225@cam.ac.uk.
  • Muraro D; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Tysoe OC; Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Sawiak S; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Beach TE; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Godfrey EM; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.
  • Upponi SS; Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Brevini T; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.
  • Wesley BT; Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Garcia-Bernardo J; Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Mahbubani K; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Canu G; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Gieseck R; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.
  • Berntsen NL; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.
  • Mulcahy VL; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Crick K; Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Fear C; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Robinson S; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.
  • Swift L; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Gambardella L; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Bargehr J; Academic Department of Medical Genetics, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Ortmann D; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Brown SE; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Osnato A; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Murphy MP; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Corbett G; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Gelson WTH; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Mells GF; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Humphreys P; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Davies SE; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Amin I; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Gibbs P; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Sinha S; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.
  • Teichmann SA; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Butler AJ; Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • See TC; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Melum E; Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Watson CJE; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Saeb-Parsy K; Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
  • Vallier L; Academic Department of Medical Genetics, University of Cambridge, Cambridge, Cambridgeshire, UK.
Science ; 371(6531): 839-846, 2021 02 19.
Article em En | MEDLINE | ID: mdl-33602855
ABSTRACT
Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças dos Ductos Biliares / Ductos Biliares / Ductos Biliares Intra-Hepáticos / Organoides / Células Epiteliais / Terapia Baseada em Transplante de Células e Tecidos Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças dos Ductos Biliares / Ductos Biliares / Ductos Biliares Intra-Hepáticos / Organoides / Células Epiteliais / Terapia Baseada em Transplante de Células e Tecidos Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article