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As age increases, the pancreas changes, which increases the risk of metabolic diseases such as type 2 diabetes, digestive disorders, and also cancer. Researchers at the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) have now been able to show in an animal model that stellate cells, in interaction with blood vessels, play a key role in age-related changes in the pancreas. They published their results in the journal Redox Biology.
The pancreas is a yellowish organ, approximately 80 to 120 grams in weight, 15 centimeters long, 5 centimeters wide, and 2-3 centimeters thick, located behind the stomach. It consists of approximately 95% of exocrine tissue, which produces digestive enzymes, and 5% of endocrine tissue, which releases the hormones insulin and glucagon to regulate blood sugar levels. In addition to these functional cells, two other cell types play an important role: Firstly, stellate cells shape the structure of the organ through the formation of the extracellular matrix. Secondly, endothelial cells form the blood vessels and are therefore essential for the blood supply of the pancreas.
With increasing age, changes leading to fat deposits (steatosis) or the pathological proliferation of connective tissue (fibrosis) can lead to cell changes in the pancreas that impair function. In particular, the formation of fat and connective tissue by stellate cells has been insufficiently investigated in relation to aging so far. Moreover, little was previously known about the role of blood vessels, which represent a kind of hub between the pancreas and the rest of the body.
Aging Research at the Cellular Level
To analyze the age-related changes in stellate cells and blood vessels of the pancreas, DIfE researchers, in collaboration with researchers from the German Center for Diabetes Research (DZD) and the European Molecular Biology Laboratory (EMBL), studied young and old mice. They isolated individual pancreatic cells and analyzed their gene expression. This single-cell transcriptomic analysis allowed them to identify different cell types and investigate their specific functions. For the precise localization of stellate cells in the pancreas and their altered distribution in old age, the researchers used immunofluorescence investigations.
New Insights into the Mechanisms of Pancreatic Fibrosis
The research team led by Dr. Marina Leer and Dr. George A. Soultoukis from the Department of Adipocyte Development and Nutrition identified different subgroups of stellate cells that form varying amounts of fat or connective tissue. With increasing age, the distribution of the identified stellate cell subgroups shifted towards a stronger tendency to fibrosis. This was accompanied by the activation of specific fibrosis-promoting signaling pathways (Transforming growth factor beta, TGFbeta and Platelet-derived growth factor, PDGF), which altered the composition of the extracellular matrix of the pancreas.
Another important finding was that the stellate cells of the aging mice interacted more strongly with the blood vessels. This cell communication caused older stellate cells to release more pro-inflammatory substances, damaging blood vessels and worsening fibrosis.
Implications for the Prevention and Treatment of Age-Related Pancreatic Diseases
"Our results suggest that pancreatic stellate cells change their identity with age and transform into fibrotic cells. These fibrotic cells contribute to the formation of scar tissue, which can impair the production of hormones and digestive enzymes," explains Soultoukis.
His colleague Leer adds: "Fibrosis and inflammation can alter the microenvironment in the pancreas and promote the development of cancer cells." The study results provide new approaches for the development of strategies for the prevention and treatment of age-related diseases of the pancreas, such as type 2 diabetes. For instance, understanding the cellular mechanisms underlying fibrosis may help to develop new drugs that slow down or reverse tissue damage.
The researchers now plan to investigate the temporal factors that influence the age-related transformation of stellate cells. In future studies, they also want to examine lifestyle factors such as diet and physical activity in more detail, which can modulate this process.
Dr. George A. Soultoukis
Postdoc Department of Adipocyte Development and Nutrition
phone: +49 33200 88 - 2451
e-mail: george.soultoukis@dife.de
Dr. Marina Leer
Postdoc Department of Adipocyte Development and Nutrition
phone: +49 33200 88 - 2115
e-mail: marina.leer@dife.de
Prof. Dr. Tim J. Schulz
Head of the Department of Adipocyte Development and Nutrition
phone: +49 33 200 88 – 2110
e-mail: tim.schulz@dife.de
Soultoukis, G. A., Leer, M., Kehm, R., Villacorta, L., Benes, V., Grune, T., Höhn, A., Schulz, T. J.: Pancreatic stellate cells have adipogenic and fibrogenic potentials but only show increased pro-fibrogenic propensity upon aging. Redox Biol. 86: 103791 (2025). [Open Access]
[DOI: https://doi.org/10.1016/j.redox.2025.103791]
Further Publication
Aga, H., Soultoukis, G., Stadion, M., Garcia-Carrizo, F., Jähnert, M., Gottmann, P., Vogel, H., Schulz, T. J., Schürmann, A.: Distinct Adipogenic and Fibrogenic Differentiation Capacities of Mesenchymal Stromal Cells from Pancreas and White Adipose Tissue. Int. J. Mol. Sci. 23(4):2108 (2022). [Open Access]
[https://doi.org/10.3390/ijms23042108]
Immunofluorescence imaging of platelet-derived growth factor α (PDGFRα) expression in exocrine areas ...
Copyright: G. Soultoukis/DIfE
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Immunofluorescence imaging of platelet-derived growth factor α (PDGFRα) expression in exocrine areas ...
Copyright: G. Soultoukis/DIfE
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