Core Viewpoint - The article discusses a groundbreaking study that successfully developed highly vascularized lung and gut organoids using human induced pluripotent stem cells (iPSCs), addressing the limitations of traditional organoid models that lack functional vascular networks and organ-specific characteristics [2][11]. Group 1: Research Background - The study was published in the journal Cell on June 30, 2025, by teams from Cincinnati Children's Hospital and UCLA, marking a significant advancement in organoid research [1]. - Prior to this research, organoids generally lacked organ-specific vascular networks, particularly in endoderm-derived organs like the lung and gut, which limited their application in disease modeling and therapeutic contexts [1][2]. Group 2: Methodology and Findings - The research established an in vitro vascularized organoid platform that accurately replicates the co-development of mesoderm and endoderm lineages, enabling efficient differentiation of endoderm-derived cells into organotypic endothelial and mesenchymal cell populations [11]. - The new method requires fewer factors for organoid development: only one inhibitor (Noggin) for lung organoids and three activators (CHIR99021, FGF4, and VEGFA) for gut organoids, allowing for spontaneous formation of vascular networks [13]. - The resulting vascularized organoids exhibited enhanced cellular diversity, improved three-dimensional structure, and physiological functions, such as tight barriers in lung organoids for gas exchange and high permeability in gut organoids for nutrient absorption [13]. Group 3: Implications for Disease Modeling - The vascularized organoids can be utilized to study abnormal intercellular interactions in various disease contexts, such as ACDMPV, a congenital lung disease caused by FOXF1 gene mutations [14]. - By differentiating patient-derived iPSCs with FOXF1 mutations into vascularized lung organoids, the study successfully replicated primary endothelial defects and secondary epithelial abnormalities associated with the disease [14]. - This platform allows for the simultaneous modeling of multi-organ interactions in diseases, providing insights into complex conditions that traditional models could not address [14][15].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 近年来，研究人员创造了各种类器官以模拟人体器官的功能，然而，一直难以构建出能够增殖且功能完备的 肝脏类器官 。这是因为，在实验室条件下， 肝脏中 的主要细胞肝细胞会发生 胆管化生，转变为胆管细胞样细胞，以平衡细胞功能和增殖之间的能量消耗，这导致肝细胞的功能最多只能维持 1-2 周。 2025 年 4 月 16 日， 庆应义塾大学医学院 佐藤俊朗 教授团队在国际顶尖学术期刊 Nature 上发表了题为 ： Generation of human adult hepatocyte organoids with metabolic functions 的研究论文。 该研究从直接取自人类患者的冷冻保存的成人肝细胞中培养出了 具有代谢功能的成人肝细胞类器官 。研究团队使用 参与炎症反应的信号蛋白 抑瘤素M （ Oncostatin-M，OSM ） 进行处理，使得肝细胞类器官的增殖量达到了百万倍，这与之前研究中的肝细胞几乎不生长的情况形成了鲜明对比。这些肝细胞类器官 持续生长了三个月，并且在半年内仍保持分化能力。这些肝细胞类器官为肝脏疾病的建模和治疗提供了新平台。 在这项最新研究中 ...