Novel Organoid Model Sheds Light on Human Pancreas Development and Disease

Researchers in the organoid group have created a new organoid that resembles the human fetal pancreas, providing an understanding of its early development. Previous organoids could not accurately replicate the three main cell types found in the pancreas, but the researchers were able to recreate a complete structure.

The team's discovery of a novel stem cell that differentiates into the three cell types is noteworthy. These results, published in the journal Cell, may aid future research into the pancreas and the creation of novel therapies for pancreatic disorders.

The two primary functions of the pancreas are blood sugar regulation and aiding food digestion.

The organ uses various cell types for each of these functions. Organoids are small, lab-grown organs about 1 mm in size and can be used to study how the pancreas functions. However until now, the majority of organoids could only consist of one kind of cell at a time, because of this, scientists find it more difficult to comprehend the pancreas as a whole.

We wanted to create an organoid that includes all the cell types found in a real pancreas. With such an organoid, we could study how these different cells interact and gain a deeper understanding of how the pancreas develops.”

Amanda Andersson Rolf, Study First Author, Hubrecht Institute

Creating a Complete Organoid

Using pancreatic tissue, Andersson Rolf and her colleagues developed a new three-dimensional organoid that mimics the human pancreas during the fetal stage. This organoid contained the three primary types of pancreatic cells: acinar, ductal, and endocrine cells. Every one of these cells is essential.

While ductal cells create channels to transport digestive enzymes to the gut, acinar cells release enzymes that aid in food digestion. Lastly, endocrine cells create hormones like insulin to regulate blood sugar levels.

In our organoid, we discovered and characterized a new type of stem cell that has the unique ability to develop into all three cell type. We saw that the three cell types not only formed but also performed their expected functions. The acinar cells released digestive enzymes and the endocrine cells produced hormones.”

Amanda Andersson Rolf, Study First Author, Hubrecht Institute

Pancreas Organoid Gives New Clues.

The researchers discovered new details about the development of the pancreas by using these organoids.

“The stem cell of the fetal pancreas is present longer than scientists have seen in earlier studies with mice,” Andersson Rolf said.

Interestingly, organoids derived from one of these stem cells can develop quickly over several years while still producing the three primary pancreatic cell types. Andersson Rolf and her associates discovered another significant distinction between the pancreatic development of mice and humans.

Andersson Rolf explained, “We saw the presence of a protein called LGR5, which marks stem cells across different tissues. This protein appears in human pancreatic stem cells but not in mice. Our research highlights the importance of studying human biology, as we could not have discovered this using animal cells”

Future Perspective

Thanks to the new organoid that resembles the fetal pancreas, scientists may be able to investigate how genes and the environment impact the development and health of the pancreas in new ways. Research on these organoids may ultimately aid in the creation of novel medications and regenerative treatments for pancreatic disorders.

However, we first need to fully understand how the cells and molecules in the human pancreas work together during development and in disease. We are just starting to scratch the surface.”

Amanda Andersson Rolf, Study First Author, Hubrecht Institute

Video Credit: Hubrecht Institute