Human pancreatic islet-derived stromal cells reveal combined features of mesenchymal stromal cells and pancreatic stellate cells

Abstract Mesenchymal stromal cells (MSCs) show great potential in the field of regenerative medicine due to their multipotent differentiation capabilities and immunomodulatory properties. However, the characterization and classification of MSCs, particularly those derived from the pancreas, remains challenging, leading to a proliferation of terminology in the literature. Here, we present a comprehensive study elucidating the successful isolation of human pancreas-derived mesenchymal stromal cells (hPD-MSCs) from pancreatic tissue, their immortalization using lentiviral transduction of hTERT, and the maintenance of characteristic spindle-shaped morphology over extended passages. Flow cytometry analysis confirms the expression of classical MSC markers CD90, CD73, CD105, and CD44, along with CD106 (VCAM-1), indicative of immunomodulatory potential. Moreover, hPD-MSCs exhibit multilineage differentiation capacity into adipogenic and osteogenic lineages. Transcriptomic analysis reveals distinct gene expression profiles, highlighting similarities to pancreatic stellate cells (PSCs) and identifying specific genes that characterize hPD-MSCs in comparison with mesenchymal cells of different origins. Notably, among these genes, hPD-MSCs exhibit differential expression in genes associated with pancreatic function, such as ISL1, and neural development (for example, NPTX1 and ZNF804A). The analysis also reveals a gene with an unknown function (ENSG00000286190). Our findings contribute to the understanding of hPD-MSCs and their potential in regenerative medicine, particularly in pancreatic pathology.