Secretome analysis of human and rat pancreatic islets co-cultured with adipose-derived stromal cells reveals a signature with enhanced regenerative capacities

Abstract

Pancreatic islet transplantation (PIT), a promising treatment for Type 1 Diabetes (T1D), encounters challenges in the pre- and post-transplantation phases. Co-culturing or co-transplantation of islets with mesenchymal stromal cells (MSC), known for their regenerative properties, emerged as a potential solution and was shown to increase islet function and improve PIT outcomes. This study explored the changes in the islets secretion signature (secretome) when co-cultured with adipose-derived stromal cells (ASC), an MSC subtype. The secretome profile of islets and co-cultures under various stressors, i.e., cytokines, high glucose, hypoxia, and a combination of hypoxia and high glucose, was investigated. The results shed light on the potential mechanisms through which ASC support islets functional survival. Co-culturing pancreatic islets with ASC induced substantial proteomic changes, impacting pathways crucial for energy metabolism, angiogenesis, extracellular matrix organization, and immune responses. The analysis of key signaling molecules (VEGF, PDGF, bFGF, Collagen I alpha 1, IL-1, and IL-10) revealed alterations influenced by the culturing conditions and the presence of the ASC. In vitro functional assays using the secretomes also demonstrated their potential to differentially influence angiogenic processes, enhance collagen deposition, and modulate the immune system based on the conditions in which they were generated. These findings offer valuable insights into the potential of ASC co-culturing to address challenges in PIT, paving the way for enhanced therapeutic interventions in T1D and regenerative medicine. HighlightsO_LIBoth in-silico and in-vitro data support that co-culturing pancreatic islets with ASC enhances islet function. C_LIO_LICo-culturing islets with ASC induces changes in the secretome, impacting pathways related to energy metabolism, angiogenesis, extracellular matrix organization, and immune response. C_LIO_LIKey signaling molecules, including VEGF, PDGF, bFGF, Collagen I alpha 1, IL-1, and IL-10, are differentially affected by various co-culturing conditions. C_LI