Working with organoids derived from mouse cells, researchers explored the processes involved in lumen formation in the pancreas and uncovered what controls the shape of lumens (fluid-filled cavities) during pancreatic development. They suggest that there are three main factors: how fast cells proliferate, the pressure inside the lumen, and the permeability of the cells around the lumen. More specifically, the shape of the lumen depends on the balance between the cell proliferation rate and the pressure in the lumen. Low pressure and high proliferation produce more complex or ‘star-shaped’ lumens. The pressure in lumens remain low because the surrounding pancreatic tissue is permeable.
The discovered mechanisms could be relevant to other organs with complex ductal systems and to common cystic diseases. Furthermore, these findings could be used to develop new therapeutic strategies, including testing the effects of drugs for diseases.
This work is published in Nature Cell Biology in the paper, “Permeability-driven pressure and cell proliferation control lumen morphogenesis in pancreatic organoids.”
Lumens in the pancreas—fluid-filled spaces which are crucial for organ function and serve as transport and delivery networks—form a complex ductal system and its channels transport digestive enzymes to the small intestine. Understanding how this system forms in embryonic development is essential, both for normal organ formation and for diagnosing and treating pancreatic disorders. Despite their importance, how lumens take certain shapes is not fully understood, as studies in other models have largely been limited to the formation of single, spherical lumens. Organoid models can exhibit a range of lumen morphologies, such as complex networks of thin tubes.
Pancreatic organoids “can form either large spherical lumen or narrow complex interconnected lumen structures, depending on the medium in the dish,” says Byung Ho Lee, PhD, postdoctoral researcher in the group of Anne Grapin-Botton, PhD director at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany. “By adding specific chemical drugs altering cell proliferation rate and pressure in the lumen, we were able to change lumen shape. We also found that making the epithelial cells surrounding the lumen more permeable reduces pressure and can change the shape of the lumen as well.”
More specifically, the authors write that “manipulating proliferation and lumen pressure can alter or reverse lumen development both in silico and in vitro. Increasing epithelial permeability reduces lumen pressure, converting from spherical to complex lumina.”
“This discovery could help us understand how other organs with narrow interconnected ducts develop and how common cystic diseases affect them,” notes Grapin-Botton. “Our model system could further research in the field of organ development and tissue engineering and also potentially be used to test how different drugs affect diseases, which could lead to new treatments. This could help us better understand and treat diseases that affect the pancreas and other organs with branching ducts.”