Cellular map of the pancreas could lead to better treatments against pancreatic cancer and diabetes

Pancreatic diseases, such as diabetes or pancreatic cancer, are usually severe and have a strong impact on patients. Unfortunately, today, there are no specific or effective treatments for pancreatic cancer, so the survival rate of patients is very low. In the case of diabetes, the development of new cell replacement therapies for insulin-producing cells seems to be the future cure of insulin-dependent patients.

Despite years of research, very little is known about the great complexity and diversity of the cells that make up the pancreas, specifically the pancreatic duct cells, which may give rise pancreatic cancer. This makes it difficult to achieve effective treatments aimed at the organ’s diseases key points.

However, if all these cells, their characteristics and how they relate to each other were well known, we could better understand the development of these diseases and design specific treatments to improve the patients’ lives, especially in those who suffer from pancreatic cancer, whose 5-year survival is less than 10%.

In this sense, a study carried out by researchers from the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Barcelona (UB), has described, with very high detail—cell by cell—the cells that make up the pancreas and its ducts.

Published in the journal Gastroenterology, the work was led by Dr. Meritxell Rovira, head of the Pancreatic Regeneration group at IDIBELL, researcher at the Department of Physiological Sciences of the UB Faculty of Medicine and Health Sciences (Bellvitge Campus) and the Program for the Clinical Translation of Regenerative Medicine of Catalonia (P-CMR[C]).

The advances obtained thanks to this study lay the foundations for the project that this researcher is developing thanks to the CRIS Excellence Program 2023.

15 new cell populations in the pancreas

The pancreas is both an exocrine and endocrine gland. Its endocrine function is to secrete various hormones into the blood flow, such as insulin and glucagon, which regulate blood glucose levels. As an exocrine gland, it secretes, through its duct, pancreatic juice to the duodenum, which contains bicarbonate and digestive enzymes.

Dr. Rovira’s team has managed to identify 15 new populations of cells in the pancreas, each of them with their behaviors and characteristics.

According to the researcher, “these results are very relevant: they can be a great starting point to better understand how pancreatic diseases, such as pancreatic cancer, develop. In addition, we have observed that duct cells have great plasticity in culture and could be used as a source of new insulin-producing cells in organoid cultures for regenerative medicine therapies in diabetes.”

Rovira says the published data lay the foundation for future studies that investigate the role of new pancreas duct cell populations in the regeneration of the organ and the pathogenesis of its exocrine function. “If we know how a disease develops,” adds Rovira, “we can design better, more precise and personalized therapies against it.”

Cell-by-cell analysis

The results of the study have been obtained using organoid cultures (or three-dimensional mini-organs), models of exocrine lesions and pancreatic cancer samples. To examine the gene expression of individual cells, the scRNA-seq (single-cell transcriptomics) technique has been used, which is capable of simultaneously measuring the RNA concentration of thousands of genes in each cell.

Thanks to these experimental approaches, it has been possible to comprehensively characterize mouse ductal heterogeneity at single-cell resolution, from the centroacinar cells to the main duct of the pancreas. Even so, the researchers clarify that new animal models are needed to investigate the results obtained in vivo and more thoroughly.

The translation of these findings to the human environment would allow, on the one hand, to identify different pancreatic duct cells involved in the origin of pancreatic cancer and, consequently, lead to a new stratification of patients based on markers and identify new therapeutic goals.

On the other hand, the results obtained in organoid cultures could lead to future cell replacement therapies for the treatment of diabetes.