Liao Yuwei, Lin Zhifan, Li Siyu, Yin Xiaolei
Acta Biochim Biophys Sin (Shanghai). 2024 Dec 5;57(7):1184-1194. doi: 10.3724/abbs.2024218.
Advancements in three-dimensional (3D) organoid cultures have created more physiologically relevant models for pancreatic disease research, but efficiently generating mature pancreatic ductal cells remains challenging. In this study, we develop a novel protocol to generate pancreatic ductal organoids (PDOs) with high initiation efficiency and an enrichment of pancreatic ductal cells. By utilizing a cocktail of small molecules, we optimize the culture conditions to improve organoid formation. Our findings demonstrate that this protocol facilitates the formation and expansion of PDOs derived from Sox9-positive ductal cells, including heterogeneous ductal cells and acinar cells. These organoid cultures exhibit remarkable stability, supporting long-term expansion. This system provides an efficient model with potential applications in high-throughput drug screening. Moreover, these organoids recapitulate the exocrine cell composition and may reflect the cellular plasticity between ductal and acinar cells, providing a valuable platform for investigating pancreatic diseases such as pancreatic ductal adenocarcinoma (PDAC). The model presents a promising tool for future research aimed at understanding disease mechanisms and potentially helping drug development for pancreatic disorders.
三维（3D）类器官培养技术的进步为胰腺疾病研究创造了更具生理相关性的模型，但高效生成成熟的胰腺导管细胞仍然具有挑战性。在本研究中，我们开发了一种新方法，以高起始效率生成胰腺导管类器官（PDO）并富集胰腺导管细胞。通过使用小分子混合物，我们优化了培养条件以促进类器官形成。我们的研究结果表明，该方法有助于源自Sox9阳性导管细胞（包括异质性导管细胞和腺泡细胞）的PDO的形成和扩增。这些类器官培养物表现出显著的稳定性，支持长期扩增。该系统提供了一个高效模型，具有在高通量药物筛选中的潜在应用。此外，这些类器官重现了外分泌细胞组成，并可能反映导管细胞和腺泡细胞之间的细胞可塑性，为研究胰腺疾病如胰腺导管腺癌（PDAC）提供了一个有价值的平台。该模型为未来旨在理解疾病机制并可能有助于胰腺疾病药物开发的研究提供了一个有前景的工具。
