Department of Surgery, Keio University School of Medicine, Shinanomachi, Shinjuku, Japan.
Institute of Materials Science and Technology (E308), Technische Universität Wien, Vienna, Austria.
PLoS One. 2024 Feb 15;19(2):e0297285. doi: 10.1371/journal.pone.0297285. eCollection 2024.
Reconstruction of the biliary system is indispensable for the regeneration of transplantable liver grafts. Here, we report the establishment of the first continuous three-dimensional biliary system scaffold for bile acid excretion using a novel method. We confirmed the preservation of the liver-derived extracellular matrix distribution in the scaffold. In addition, hepatocyte progenitors decellularized via the bile duct by slow-speed perfusion differentiated into hepatocyte- and cholangiocyte-like cells, mimicking hepatic cords and bile ducts, respectively. Furthermore, qRT-PCR demonstrated increased ALB, BSEP, and AQP8 expression, revealing bile canaliculi- and bile duct-specific genetic patterns. Therefore, we concluded that locally preserved extracellular matrices in the scaffold stimulated hepatic progenitors and provided efficient differentiation, as well as regeneration of a three-dimensional continuous biliary system from hepatic cords through bile ducts. These findings suggest that organ-derived scaffolds can be utilized for the efficient reconstruction of functional biliary systems.
胆道系统的重建对于可移植肝移植物的再生是必不可少的。在这里，我们报告了使用一种新方法建立第一个用于胆汁酸排泄的连续三维胆道系统支架。我们证实了支架中保留了肝来源的细胞外基质分布。此外，通过慢速灌注胆管脱细胞的肝祖细胞分化为肝样细胞和胆管样细胞，分别模拟肝索和胆管。此外，qRT-PCR 显示 ALB、BSEP 和 AQP8 的表达增加，揭示了胆小管和胆管特异性的遗传模式。因此，我们得出结论，支架中局部保留的细胞外基质刺激肝祖细胞，并提供有效的分化，以及通过胆管从肝索再生三维连续胆道系统。这些发现表明，器官来源的支架可用于有效重建功能性胆道系统。
