Liver organoids have gained much attention in recent years for their potential applications to liver disease modeling and pharmacologic drug screening. Liver organoids produced in vitro reflect some aspects of the in vivo physiological and pathological conditions of the liver. However, the generation of liver organoids with perfusable luminal vasculature remains a major challenge, hindering precise and effective modeling of liver diseases. Furthermore, vascularization is required for large organoids or assembloids to closely mimic the complexity of tissue architecture without cell death in the core region. A few studies have successfully generated liver organoids with endothelial cell networks, but most of these vascular networks produced luminal structures after being transplanted into tissues of host animals. Therefore, formation of luminal vasculature is an unmet need to overcome the limitation of liver organoids as an in vitro model investigating different acute and chronic liver diseases. Here, we provide an overview of the unique features of hepatic vasculature under pathophysiological conditions and summarize the biochemical and biophysical cues that drive vasculogenesis and angiogenesis in vitro. We also highlight recent progress in generating vascularized liver organoids in vitro and discuss potential strategies that may enable the generation of perfusable luminal vasculature in liver organoids.

中文翻译：

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肝脏类器官管腔血管的体外生成：从基础血管生物学到血管化肝类器官。

近年来，肝脏类器官因其在肝病建模和药理药物筛选中的潜在应用而备受关注。体外产生的肝脏类器官反映了肝脏在体内某些方面的生理和病理状况。然而，具有可灌注管腔血管的肝脏类器官的产生仍然是一个重大挑战，阻碍了肝脏疾病的精确和有效建模。此外，大型类器官或组合体需要血管形成，以密切模拟组织结构的复杂性，而不会在核心区域发生细胞死亡。一些研究已经成功地产生了具有内皮细胞网络的肝脏类器官，但这些血管网络中的大多数在被移植到宿主动物的组织中后产生了管腔结构。因此，管腔脉管系统的形成是克服肝脏类器官作为体外研究的局限性的未满足需求研究不同急性和慢性肝病的模型。在这里，我们概述了肝脏脉管系统在病理生理条件下的独特特征，并总结了在体外驱动血管发生和血管生成的生化和生物物理学线索。我们还强调了在体外生成血管化肝脏类器官方面的最新进展，并讨论了可能能够在肝脏类器官中生成可灌注管腔血管系统的潜在策略。