人类“迷你肝”再进化！西湖大学校友Nature论文：构建首个可长期维持的多细胞人源肝脏类器官组装体

Core Viewpoint - The article discusses the significant advancements in liver organoid research, highlighting the challenges of replicating the complex multicellular structure and function of adult human liver in vitro [1][2]. Group 1: Challenges in Liver Organoid Models - A core challenge in creating adult liver organoids is maintaining the multicellular complexity found in real human livers, which consist of various cell types working together [2][4]. - Existing models, such as primary human hepatocytes (PHH) and iPSC-derived liver organoids, face limitations in long-term functionality and physiological relevance [4][6]. Group 2: Breakthrough in Human Liver Assemblage - A research team from the Max Planck Institute successfully created a human liver "assembloid" model that replicates the multicellular structure and functional characteristics of the periportal region of the liver [7]. - This model was developed using fresh liver tissues from 28 adult donors, ensuring stability and enhancing clinical relevance [12]. Group 3: Advancements in Cell Culture Techniques - The research team optimized the culture system to support the long-term expansion of human liver cells, achieving a mature liver-like function [14][16]. - The model demonstrated the ability to replicate liver structures, including bile duct networks, and showed significant improvements in drug metabolism and other liver functions [17][19]. Group 4: Disease Modeling Capabilities - The human liver assembloid can simulate both healthy and diseased states, successfully inducing early cholangiopathy-like changes, which provides a novel model for studying cholangiopathy and related liver diseases [22]. Group 5: Future Prospects - This research fills a gap in existing 3D human liver models by enhancing structural complexity, cellular diversity, and functional maturity, with potential applications in drug screening, toxicity assessment, and personalized medicine [24]. - Future developments may include integrating additional cell types to create a more comprehensive human liver model that closely resembles real human physiology [24].