Researchers Develop Protocol to Create Functional Acinar Cells in Organoids
Scientists have made a groundbreaking discovery in the field of organoid research, developing a protocol to create functional acinar cells within miniature organ models. These organoids, grown in a dish, mimic the structure and function of human organs, offering a valuable tool for studying development, regeneration, and disease. By engineering patient cells or using genetic manipulation, researchers can explore the impact of specific proteins and their variations on these processes.
However, current methods for studying multiple genes simultaneously have limitations. They fail to provide a comprehensive understanding of how cells adapt and move in response to genetic and molecular changes. High-content image-based screens offer a more detailed solution, but their implementation and data analysis present challenges.
A team of researchers led by Anne Grapin-Botton, a director at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, and an honorary professor at TU Dresden, has developed a novel system. This system utilizes pancreatic organoids, composed of human pancreatic progenitor cells, to simultaneously test numerous compounds (molecules). Through high-content image-based screening and quantitative multivariate analysis, the researchers identified changes in the cells.
From Sphere to Rosette Shape
The study's lead author, Rashmiparvathi Keshara, a former doctoral student in Anne Grapin-Botton's group, explains that they screened 538 compounds and found 54 with significant effects on pancreas progenitor organoids. Keshara focused on compounds affecting cell identity and organoid shape, identifying inhibitors of the GSK3A/B protein. When inhibited, the WNT signaling pathway is activated, leading to the expression of acinar cell genes. While gene expression increased, the cells did not fully differentiate into acinar cells. To achieve acinar cell differentiation, the researchers optimized the growth medium.
The removal of the growth factor FGF further enhanced organoid differentiation and the formation of rosette-like structures, a characteristic of acinar cells in living organisms, according to Karolina Kuodyte, a postdoctoral researcher in the Grapin-Botton group.
Functional Pancreatic Acinar Cells
Using electron microscopy, the researchers discovered tiny vesicles inside the cells, a hallmark of enzyme-producing pancreatic acinar cells. They then confirmed the functionality of these acinar cells by detecting the production of essential enzymes like amylase and trypsin, crucial for digestion.
Anne Grapin-Botton expresses excitement about presenting a protocol for developing human acinar cells with unprecedented functionality in a human pancreas organoid. This simple protocol, with minimal components, has the potential to advance our understanding of pancreas development and may lead to new therapeutic targets for pancreatic cancer. The researchers plan to further investigate human pancreatic cancer initiation using their innovative system.
Source: Keshara, R., et al. (2026). High-content screening of organoids reveals the mechanisms of human pancreas acinar specification. Cell Stem Cell. doi: 10.1016/j.stem.2025.12.023. https://www.sciencedirect.com/science/article/pii/S1934590925004576?via%3Dihub
