دورية أكاديمية
Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.
| العنوان: | Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. |
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| المؤلفون: | Sampaziotis F; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK. fs347@cam.ac.uk lv225@cam.ac.uk.; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.; Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Muraro D; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Tysoe OC; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK., Sawiak S; Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK., Beach TE; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK., Godfrey EM; Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Upponi SS; Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Brevini T; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Wesley BT; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Garcia-Bernardo J; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK., Mahbubani K; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK., Canu G; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Gieseck R 3rd; Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Berntsen NL; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Mulcahy VL; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.; Academic Department of Medical Genetics, University of Cambridge, Cambridge, Cambridgeshire, UK., Crick K; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Fear C; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Robinson S; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Swift L; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Gambardella L; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK., Bargehr J; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK., Ortmann D; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Brown SE; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Osnato A; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Murphy MP; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, Cambridgeshire, UK., Corbett G; Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Gelson WTH; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.; Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Mells GF; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.; Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.; Academic Department of Medical Genetics, University of Cambridge, Cambridge, Cambridgeshire, UK., Humphreys P; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK., Davies SE; Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Amin I; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Gibbs P; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Sinha S; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK.; Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK., Teichmann SA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, Cambridgeshire, UK., Butler AJ; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., See TC; Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Melum E; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway., Watson CJE; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.; National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU), Cambridge, Cambridgeshire, UK.; University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, Cambridgeshire, UK., Saeb-Parsy K; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.; Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK., Vallier L; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, Cambridgeshire, UK. fs347@cam.ac.uk lv225@cam.ac.uk.; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK. |
| المصدر: | Science (New York, N.Y.) [Science] 2021 Feb 19; Vol. 371 (6531), pp. 839-846. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
| مواضيع طبية MeSH: | Cell- and Tissue-Based Therapy*, Bile Duct Diseases/*therapy , Bile Ducts/*cytology , Bile Ducts, Intrahepatic/*physiology , Epithelial Cells/*cytology , Organoids/*transplantation, Animals ; Bile ; Bile Ducts/physiology ; Bile Ducts, Intrahepatic/cytology ; Common Bile Duct/cytology ; Epithelial Cells/physiology ; Gallbladder/cytology ; Gene Expression Regulation ; Humans ; Liver/physiology ; Liver Transplantation ; Mesenchymal Stem Cell Transplantation ; Mice ; Organoids/physiology ; RNA-Seq ; Tissue and Organ Procurement ; Transcriptome |
| مستخلص: | 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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
| التعليقات: | Comment in: Science. 2021 Feb 19;371(6531):786-787. (PMID: 33602846) Comment in: Nat Rev Gastroenterol Hepatol. 2021 Jun;18(6):371-372. (PMID: 33948023) Comment in: Transplantation. 2021 Sep 1;105(9):1886-1887. (PMID: 34416748) |
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| معلومات مُعتمدة: | MC_PC_17230 United Kingdom MRC_ Medical Research Council; PG/17/24/32886 United Kingdom BHF_ British Heart Foundation; NC/T2T0419 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research; G0701448 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; 203151 United Kingdom WT_ Wellcome Trust; NC/N001540/1 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research; MC_UU_12012/5 United Kingdom MRC_ Medical Research Council; FS/18/46/33663 United Kingdom BHF_ British Heart Foundation |
| تواريخ الأحداث: | Date Created: 20210219 Date Completed: 20210308 Latest Revision: 20230201 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7610478 |
| DOI: | 10.1126/science.aaz6964 |
| PMID: | 33602855 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1095-9203 |
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| DOI: | 10.1126/science.aaz6964 |