Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
J Cell Mol Med. 2022 Oct;26(19):4949-4958. doi: 10.1111/jcmm.17510. Epub 2022 Aug 26.
In Europe alone, each year 5500 people require a life-saving liver transplantation, but 18% die before receiving one due to the shortage of donor organs. Whole organ engineering, utilizing decellularized liver scaffolds repopulated with autologous cells, is an attractive alternative to increase the pool of available organs for transplantation. The development of this technology is hampered by a lack of a suitable large-animal model representative of the human physiology and a reliable and continuous cell source. We have generated porcine intrahepatic cholangiocyte organoids from adult stem cells and demonstrate that these cultures remained stable over multiple passages whilst retaining the ability to differentiate into hepatocyte- and cholangiocyte-like cells. Recellularization onto porcine scaffolds was efficient and the organoids homogeneously differentiated, even showing polarization. Our porcine intrahepatic cholangiocyte system, combined with porcine liver scaffold paves the way for developing whole liver engineering in a relevant large-animal model.
仅在欧洲，每年就有 5500 人需要进行挽救生命的肝移植，但由于供体器官短缺，18%的人在接受移植前死亡。利用去细胞化的肝支架重新填充自体细胞的全器官工程是增加可用于移植的器官库的一种有吸引力的替代方法。该技术的发展受到缺乏合适的大动物模型来代表人类生理学以及可靠和持续的细胞来源的阻碍。我们已经从成年干细胞中生成了猪肝内胆管细胞类器官，并证明这些培养物在多次传代过程中保持稳定，同时保留了分化为肝细胞和胆管细胞样细胞的能力。在猪支架上的再细胞化是有效的，类器官均匀分化，甚至显示出极化。我们的猪肝内胆管细胞系统与猪肝支架相结合，为在相关大动物模型中开发全肝工程铺平了道路。
