PDF(Pubmed)
Abstract：
Liver is involved in metabolic reactions, ammonia detoxification, and immunity. Multicellular liver tissue cultures are more desirable for drug screening, disease modeling, and researching transplantation therapy, than hepatocytes monocultures. Hepatocytes monocultures are not stable for long. Further, hepatocyte-like cells induced from pluripotent stem cells and in vivo hepatocytes are functionally dissimilar. Organoid technology circumvents these issues by generating functional ex vivo liver tissue from intrinsic liver progenitor cells and extrinsic stem cells, including pluripotent stem cells. To function as in vivo liver tissue, the liver organoid cells must be arranged precisely in the 3-dimensional space, closely mimicking in vivo liver tissue. Moreover, for long term functioning, liver organoids must be appropriately vascularized and in contact with neighboring epithelial tissues (e.g., bile canaliculi and intrahepatic bile duct, or intrahepatic and extrahepatic bile ducts). Recent discoveries in liver developmental biology allows one to successfully induce liver component cells and generate organoids. Thus, here, in this review, we summarize the current state of knowledge on liver development with a focus on its application in generating different liver organoids. We also cover the future prospects in creating (functionally and structurally) in vivo-like liver organoids using the current knowledge on liver development.
摘要：
肝脏参与代谢反应，氨解毒,和豁免权。多细胞肝组织培养更适合用于药物筛选，疾病建模,研究移植疗法，比肝细胞单一培养。肝细胞单一培养物不能长期稳定。Further,多能干细胞诱导的肝细胞样细胞和体内肝细胞在功能上不同。类器官技术通过从内在肝祖细胞和外在干细胞产生功能性离体肝组织来规避这些问题。包括多能干细胞。作为体内肝脏组织，肝脏类器官细胞必须精确地排列在三维空间中，密切模仿体内肝组织。此外，为了长期运作，肝类器官必须适当地血管化并与邻近的上皮组织接触(例如，胆管和肝内胆管，或肝内和肝外胆管）。肝脏发育生物学的最新发现使人们能够成功地诱导肝脏成分细胞并产生类器官。因此，在这里，在这次审查中,我们总结了肝脏发育的知识现状，重点是其在生成不同肝脏类器官中的应用。我们还涵盖了使用当前的肝脏发育知识创建（功能和结构）体内肝类器官的未来前景。
