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

doi:10.1126/science.aaz6964

GSTDTAP > 气候变化

DOI	10.1126/science.aaz6964
	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
	2021-02-19
发表期刊	Science
出版年	2021
英文摘要	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][1]; see also p. [786][2] 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. [1]: /lookup/doi/10.1126/science.aaz6964 [2]: /lookup/doi/10.1126/science.abg3179
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/315731
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Fotios Sampaziotis,Daniele Muraro,Olivia C. Tysoe,et al. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver[J]. Science,2021.
APA	Fotios Sampaziotis.,Daniele Muraro.,Olivia C. Tysoe.,Stephen Sawiak.,Timothy E. Beach.,...&Ludovic Vallier.(2021).Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.Science.
MLA	Fotios Sampaziotis,et al."Cholangiocyte organoids can repair bile ducts after transplantation in the human liver".Science (2021).