Mesenchymal Cells Appearing in Pancreatic Tissue Culture Are Bone Marrow-Derived Stem Cells With the Capacity to Improve Transplanted Islet Function

• DOI: 10.1002/stem.259
• Publication Date: 2009-11-19T00:20:37Z
• Authors: Valeria Sordi; Raffaella Melzi; Alessia Mercalli; Roberta Formicola; Claudio Doglioni; Francesca Tiboni; Giuliana Ferrari; Rita Nano; Karolina Chwalek; Eckhard Lammert; Ezio Bonifacio; Lorenzo Piemonti
• Keywords: Blood Glucose; 0301 basic medicine; Green Fluorescent Proteins; Mesenchymal cells; Pancreatic tissue; 610; Bone Marrow Cells; Diabetes Mellitus, Experimental; 1307 Cell Biology; 1309 Developmental Biology; Islets of Langerhans; 03 medical and health sciences; Antigens, CD; Cell Movement; Insulin-Secreting Cells; Animals; Humans; AC133 Antigen; Angiogenic Proteins; 5'-Nucleotidase; Cells, Cultured; Bone Marrow Transplantation; Cell Proliferation; Glycoproteins; Endothelial Cells; Gene Expression Regulation, Developmental; Cell Differentiation; Islet function; 1313 Molecular Medicine

Abstract Adherent fibroblast-like cells have been reported to appear in cultures of human endocrine or exocrine pancreatic tissue during attempts to differentiate human β cells from pancreatic precursors. A thorough characterization of these mesenchymal cells has not yet been completed, and there are no conclusive data about their origin. We demonstrated that the human mesenchymal cells outgrowing from cultured human pancreatic endocrine or exocrine tissue are pancreatic mesenchymal stem cells (pMSC) that propagate from contaminating pMSC. The origin of pMSC is partly extrapancreatic both in humans and mice, and by using green fluorescent protein (GFP+) bone marrow transplantation in the mouse model, we were able to demonstrate that these cells derive from the CD45+ component of bone marrow. The pMSC express negligible levels of islet-specific genes both in basal conditions and after serum deprivation or exogenous growth factor exposure, and might not represent optimal candidates for generation of physiologically competent β-cells. On the other hand, when cotransplanted with a minimal pancreatic islet mass, pMSC facilitate the restoration of normoglycemia and the neovascularization of the graft. These results suggest that pMSCs could exert an indirect role of “helper” cells in tissue repair processes.