Scientists Uncover How Cell Growth and Pressure Shape Pancreatic Ducts

Researchers have discovered that pressure and the rate of cell division work together to shape the fluid-filled cavities in the developing pancreas.

Organs often have fluid-filled spaces called lumens, which are crucial for organ function and serve as transport and delivery networks.

Lumens in the pancreas 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 for both 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, which more closely mimic the physiological characteristics of real organs, can exhibit a range of lumen morphologies, such as complex networks of thin tubes.

Researchers in Anne Grapin-Botton’s group at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany - where she also serves as an Honorary Professor at TU Dresden - joined forces with international colleagues to better understand how complex lumens form.

They worked closely with teams led by Masaki Sano at the University of Tokyo (Japan), Tetsuya Hiraiwa at the Institute of Physics of Academia Sinica (Taiwan), and Daniel Rivéline at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (France).

By combining computational models with lab-based experiments, the scientists pinpointed the key factors that shape these intricate fluid-filled cavities.

Star-Shaped Lumen Resembles Real Pancreas

Three-dimensional pancreatic structures, also called pancreatic organoids, can form either large spherical lumen or narrow complex interconnected lumen structures, depending on the medium in the dish.

 Byung Ho Lee, Study Lead Author and Postdoctoral Researcher, Max Planck Institute of Molecular Cell Biology and Genetics

“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,” added Byung Ho Lee.

Kana Fuji, doctoral student in the research group of Masaki Sano added, “Our model can measure and predict which parameters account for the transitions of the lumen shapes, enabling feedback into the experiments themselves.”

To understand how individual cells grow and divide (and how these behaviors influence lumen formation), the research team used a mathematical model alongside their experiments to simulate the process.

Our study shows that the shape and structure of the lumen in pancreatic organoids depend on three main factors: how fast cells proliferate, the pressure inside the lumen, and how permeable the cells around the lumen are.

Anne Grapin-Botton, Director, Max Planck Institute of Molecular Cell Biology and Genetics

Grapin-Botton supervised the study together with Byung Ho Lee.

“This discovery could help us understand how other organs with narrow interconnected ducts develop and how common cystic diseases affect them. 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,” said Anne Grapin-Botton.