Researchers from the Organoid group, previously known as the Clevers group, at the Hubrecht Institute have achieved a major scientific milestone. They have developed a revolutionary organoid that closely mimics the human fetal pancreas, providing a clearer understanding of its early developmental stages. This innovation stands apart from earlier models as it includes all three key cell types of the pancreas—an accomplishment that previous organoids were unable to achieve.
The team’s work also led to the discovery of a novel stem cell capable of developing into these three essential pancreatic cell types. This discovery, published in Cell on December 2, offers a promising avenue for advancing research into pancreatic diseases and their treatment.
The pancreas plays a crucial role in the body, with its primary functions being food digestion and blood sugar regulation. These tasks are managed by specialized cell types within the organ. Traditional organoid models, which are laboratory-grown mini-organs, have fallen short by replicating only one cell type at a time. This limitation hindered comprehensive research into pancreatic function and development.
Lead researcher Amanda Andersson Rolf explained the motivation behind this groundbreaking study: “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.”
Using pancreatic tissue, the researchers successfully developed a three-dimensional organoid that represents the human pancreas in its fetal stage. This organoid includes acinar cells, ductal cells, and endocrine cells, each of which serves vital functions in the pancreas.
Acinar cells secrete enzymes necessary for breaking down food, ductal cells form channels that transport these enzymes to the gut, and endocrine cells produce hormones such as insulin to regulate blood sugar levels.
Andersson Rolf elaborated on their findings: “In our organoid, we discovered and characterized a new type of stem cell that has the unique ability to develop into all three cell types. 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.”
This cutting-edge organoid model also provided fresh insights into the developmental process of the pancreas. For instance, the team observed that fetal pancreatic stem cells persist longer in humans than previously observed in studies with mice. This discovery highlights key differences between human and mouse biology, emphasizing the importance of studying human-specific models.
Another critical finding was the presence of the protein LGR5, which is a marker for stem cells across various tissues. Interestingly, this protein was found in human pancreatic stem cells but is absent in mice, further underscoring the uniqueness of human pancreatic development.
As Andersson Rolf remarked, “Our research highlights the importance of studying human biology, as we couldn’t have discovered this using animal cells.”
This novel organoid model not only offers a more accurate representation of human pancreatic development but also opens up new research possibilities. By studying these organoids, scientists can explore how genetic and environmental factors influence the pancreas’s health and development.
The long-term potential of this research is immense. It could pave the way for regenerative therapies and innovative drugs to treat pancreatic diseases. However, significant work remains to fully understand the complex interactions between cells and molecules within the pancreas during development and disease.
This breakthrough represents a significant step forward in the field of organoid research and underscores the potential of human-based studies to revolutionize our understanding of complex organs like the pancreas.