Researchers have created a novel organoid that closely resembles the human fetal pancreas, providing insights into its early formation. This new organoid successfully replicates a complete structure encompassing the three essential cell types found in the pancreas, a feat not achieved by earlier organoids.
Scientists from the Organoid group (formerly the Clevers group) at the Hubrecht Institute have crafted an innovative organoid that simulates the human fetal pancreas, allowing for a better understanding of its initial development. This organoid recreates a full structure containing the three primary cell types present in the pancreas, which previous attempts could not fully achieve. Remarkably, the team discovered a new type of stem cell capable of giving rise to all three cell types. Their findings, published in Cell on December 2nd, aim to enhance our comprehension of pancreatic biology and pave the way for new medical treatments for pancreatic disorders in the future.
The pancreas serves two crucial functions: aiding in food digestion and regulating blood sugar levels. Each of these tasks is performed by different types of cells within the organ. Researchers can examine the pancreas’s functions by studying organoids—tiny lab-grown models about 1 mm in size. However, most existing organoids have only consisted of one cell type at a time, complicating scientists’ ability to grasp the pancreas’s overall function. “We aimed to develop an organoid that incorporates all the cell types found in a natural pancreas,” explains Amanda Andersson Rolf, the study’s lead author. “With this organoid, we could investigate how these diverse cells interact and gain a better understanding of pancreatic development.”
Constructing a complete organoid
Andersson Rolf and her team utilized pancreatic tissue to build a new three-dimensional organoid that mirrors the fetal human pancreas. This organoid included the three primary types of pancreatic cells: acinar cells, ductal cells, and endocrine cells. Each of these cell types has a distinct and vital function. Acinar cells produce enzymes that help digest food, ductal cells create pathways to transport these enzymes to the intestine, and endocrine cells generate hormones, such as insulin, that regulate blood sugar levels.
“Within our organoid, we identified and characterized a new kind of stem cell that possesses the remarkable capability to differentiate into all three cell types,” Andersson Rolf continues. “We observed that not only were the three cell types formed, but they also executed their expected roles. The acinar cells successfully released digestive enzymes, while the endocrine cells produced hormones.”
Insights from the pancreas organoid
Through the use of these organoids, the researchers gained fresh insights into pancreatic development. “The stem cell in the fetal pancreas exists for a longer duration than what has been noted in previous studies with mice,” remarks Andersson Rolf. Intriguingly, the organoids derived from one of these stem cells can grow swiftly over several years while still maintaining the ability to yield the three primary pancreatic cell types. Additionally, Andersson Rolf and her colleagues uncovered a significant difference in pancreatic development between humans and mice. “We identified a protein called LGR5, which is indicative of stem cells in various tissues. This protein is present in human pancreatic stem cells but absent in mice,” explains Andersson Rolf. “Our research emphasizes the necessity of investigating human biology, as these findings couldn’t have been detected using animal cells,” she adds.
Looking ahead
The newly developed organoid that simulates the fetal pancreas could open new pathways for researchers to explore how genetic factors and environmental influences affect pancreatic health and development. Ultimately, examining these organoids might lead to advancements in regenerative therapies and new treatments for pancreatic diseases. “However, we must first thoroughly comprehend the interplay of cells and molecules in the human pancreas during its development and in various diseases,” Andersson Rolf notes. “We are only beginning to scratch the surface.”
