英国剑桥大学Ludovic Vallier和Kourosh Saeb-Parsy研究团队合作取得一项新成果。经过不懈努力，他们发现胆管类器官可在植入人肝后修复胆管。相关论文于2021年2月19日发表在国际学术期刊《科学》杂志上。

研究人员在胆管病的背景下使用胆管细胞类器官解决了这一难题，其是肝移植的关键难题。使用单细胞RNA测序，研究人员发现原代人胆管细胞在类器官培养中丢失了转录多样性。然而，胆管细胞类器官在移植回胆管时仍保持可塑性并恢复其体内特征。

随后，研究人员利用细胞移植模型在离体常温灌注的人类肝脏中进行了验证，以证明该特性可帮助肝外类器官在移植后修复人肝内导管。该研究结果揭示了胆管细胞类器官修复人胆道上皮的机制。

据了解，类器官技术在再生医学方面具有广阔的应用前景，但尚未应用于人类。

附：英文原文

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

Author: 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

Issue&Volume: 2021/02/19

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.

DOI: 10.1126/science.aaz6964

Source: https://science.sciencemag.org/content/371/6531/839