title: Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function.
abstract: Adherent fibroblast-like cells have been reported to appear in cultures of human endocrine or exocrine pancreatic tissue during attempts to differentiate human beta 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 beta-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.
authors.affiliation: San Raffaele Diabetes Research Institute, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Sordi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Melzi
authors.forename: Alessia
authors.initials: A
authors.lastname: Mercalli
authors.forename: Roberta
authors.initials: R
authors.lastname: Formicola
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Francesca
authors.initials: F
authors.lastname: Tiboni
authors.forename: Giuliana
authors.initials: G
authors.lastname: Ferrari
authors.forename: Rita
authors.initials: R
authors.lastname: Nano
authors.forename: Karolina
authors.initials: K
authors.lastname: Chwalek
authors.forename: Eckhard
authors.initials: E
authors.lastname: Lammert
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Danielle
authors.initials: D
authors.lastname: Borg
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
mesh_terms: D015720:5'-Nucleotidase / Q000032:analysis; D000071916:AC133 Antigen; D042501:Angiogenic Proteins; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery; D042783:Endothelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000032:analysis; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D016381:Islets of Langerhans Transplantation; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000032:analysis; D013997:Time Factors
chemical_list: D000071916:AC133 Antigen; D042501:Angiogenic Proteins; D015703:Antigens, CD; D001786:Blood Glucose; D006023:Glycoproteins; D010455:Peptides; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens; D015720:5'-Nucleotidase