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].