Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts
Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts
复制标题
肝导管类器官在脱细胞肝移植物中重建肝内胆管树
DOI：
10.1016/j.biomaterials.2022.121614
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发表时间：
2022
期刊：
影响因子：
14
通讯作者：
Hatano Etsuro
中科院分区：
文献类型：
--
作者：
Tomofuji Katsuhiro;Fukumitsu Ken;Kondo Jumpei;Horie Hiroshi;Makino Kenta;Wakama Satoshi;Ito Takashi;Oshima Yu;Ogiso Satoshi;Ishii Takamichi;Inoue Masahiro;Hatano Etsuro
天然器官脱细胞三维支架是一种很有前途的工程肝移植技术，可以克服目前供体器官短缺的问题。然而，有限的胆管细胞来源和生物工程肝移植中不适当的细胞分布阻碍了它们的实际应用。类器官技术有望成为推动再生医学发展的重要工具。在本研究中，我们用肝导管类器官重建大鼠去细胞肝移植物的肝内胆管。利用体外灌流培养系统，我们展示了重建的小鼠肝类器官的胆道特征，这些器官维持了胆管标记，并重建了具有管腔结构的胆道树状网络。我们还建立了一种与工程胆管和原代肝细胞共再细胞化的方法，揭示了模拟天然肝脏的适当细胞分布。然后我们在人类类器官中使用该模型来展示重建的胆管。我们的研究结果表明，肝导管类器官是使用三维支架的生物工程肝移植物胆管的潜在细胞来源。
Three-dimensional scaffolds decellularized from native organs are a promising technique to establish engineered liver grafts and overcome the current shortage of donor organs. However, limited sources of bile duct cells and inappropriate cell distribution in bioengineered liver grafts have hindered their practical application. Organoid technology is anticipated to be an excellent tool for the advancement of regenerative medicine. In the present study, we reconstructed intrahepatic bile ducts in a rat decellularized liver graft by recellularization with liver ductal organoids. Using anex vivoperfusion culture system, we demonstrated the biliary characteristics of repopulated mouse liver organoids, which maintained bile duct markers and reconstructed biliary tree-like networks with luminal structures. We also established a method for the co-recellularization with engineered bile ducts and primary hepatocytes, revealing the appropriate cell distribution to mimic the native liver. We then utilized this model in human organoids to demonstrate the reconstructed bile ducts. Our results show that liver ductal organoids are a potential cell source for bile ducts from bioengineered liver grafts using three-dimensional scaffolds.