Uncovering the Unique Way the Pancreas Regenerates

The Context: Stem cells play a critical role in regenerating many of our organs  — when old cells are damaged or die off, stem cells provide a source for replacing them. Understanding how organs regenerate is key for treating degenerative diseases, but has remained elusive for the pancreas.

The Study: All cells in the pancreas that produce digestive enzymes and transport them to the gut — known as acinar and ductal cells — can contribute to its regenerative capacity, finds a new study performed in mice and published in Cell Stem Cell by NYSCF – Robertson Stem Cell Investigator Louis Vermeulen, MD, PhD, of Amsterdam University Medical Centers and the Oncode Institute.

Why it Matters: This study points to new mechanisms for regenerating the pancreas that don’t involve stem cells, which could inform our understanding of how pancreatic cancer develops. Further studies will illuminate whether this ability is reflected in human cells and its implications for diabetes and regenerative medicine.

“We know, for example, that new tissue is continuously being created in the intestine and that this process always starts in stem cells that are nested in the intestine,” noted Dr. Vermeulen in an article from Amsterdam UMC. “This process is essential for keeping the organ healthy, but it is often also at the root of the development of cancer.”

Dr. Vermeulen’s team decided to take a closer look at how cells regenerate in the pancreas, finding that all acinar and ductal cells – cells that produce digestive enzymes and transport them to the gut – actually contribute to this process.

“We were surprised to see in our experimental mouse models that all cells in the exocrine pancreas have the ability to repair the organ,” remarked Dr. Vermeulen.

Patiently Watching the Pancreas

“We knew in advance that this experiment would be an exercise in patience,” said Maarten Bijlsma, PhD, Associate Professor at Amsterdam University Medical Centers and co-author on the study. “Compared to the intestines, the speed at which tissue is renewed in the pancreas is much lower.”

The team used special fluorescent proteins to highlight cells in the pancreases of mice and track the cells’ behavior.

“The strength of our model is that a fluorescent protein is spontaneously activated in random cells,” explained Dr. Bijlsma. “So we can do our experiments without exposing the animals to treatments that often affect the pancreas on their own. We can then use microscopic images to map out very precisely what happens to these cells under normal conditions.”

Surprisingly, the scientists found that every acinar and ductal cell in the pancreas can contribute to its regenerative capacity.

“After careful analysis and mathematical modelling, we were surprised that we did not find any evidence for the existence of stem cells in the pancreas. In fact, everything now indicates that all cells that make digestive enzymes and transport them to the gut in the pancreas have so-called regenerative capacities.”

Basic Research Lead to Better Treatments

Next, the team will explore whether human acinar and ductal cells carry this regenerative capacity in the same way mouse cells do. 

Dr. Vermeulen also stresses that understanding the dynamics of cells in the pancreas will help researchers understand where these processes start to falter in cancer patients, opening the door for development of new treatments. The team will also begin studying the intricacies of regeneration in other organs including the skin, stomach, and esophagus.

“On average, almost 90% of people who receive a pancreatic cancer diagnosis die within a few years,” he said. “Truly groundbreaking innovation in drug research often stems from fundamental knowledge. We hope that our basic research will open up new avenues and thus provide a starting point for finding new treatments for pancreatic cancer.”

Journal Article:

Continuous clonal labeling reveals uniform progenitor potential in the adult exocrine pancreas

Sophie C. Lodestijn, Tom van den Bosch, Lisanne E. Nijman, Leandro F. Moreno, Sophie Schlingemann, Vivek M. Sheraton, Sanne M. van Neerven, Jasper J. Koning, Felipe A. Vieira Braga, Nanne J. Paauw, Maria C. Lecca, Kristiaan J. Lenos, Edward Morrissey, Daniël M. Miedema, Douglas J. Winton, Maarten F. Bijlsma, Louis Vermeulen. Cell Stem Cell. 2021. DOI: https://doi.org/10.1016/j.stem.2021.07.004