Salivary Gland Cells as a Promising Cell Therapy Source for Diabetes: Analysis of Signaling Pathways and Intercellular Interactions with Mouse Pancreatic Cells, in Comparison with MSCs

Pancreatic islets play a central role in glucose homeostasis, and their dysfunction underlies the development of diabetes mellitus. While mesenchymal stromal cells (MSCs) have shown promise in supporting islet regeneration, limitations such as immunogenicity and invasiveness prompt the search for alternative sources. Salivary gland cells (SGCs), due to their accessibility and regenerative potential, are emerging as a candidate, though their role in pancreatic repair remains largely unexplored. This study evaluated the interactions of MSCs and SGCs with pancreatic islets using in vitro co-culture models, migration assays, apoptosis and proliferation analysis of HIT-T15 β-cells, and proteomic profiling. Both MSCs and SGCs demonstrated chemotactic responses to islet-derived factors. Co-culture with MSCs enhanced β-cell proliferation and reduced apoptosis, while SGCs increased proliferation without significant anti-apoptotic effects. Proteomic analysis and ligand-receptor mapping revealed that MSCs primarily influenced extracellular matrix remodeling and immunomodulation, whereas SGCs were enriched in adhesion and intercellular signaling pathways. Key pathways included collagen-integrin interactions, fibronectin signaling, and PECAM1-associated vascular support. These results indicate that SGCs, despite functional differences, possess regenerative properties comparable to MSCs and represent a promising alternative for cell-based support of pancreatic islets in diabetes therapy and transplantation contexts.