title: Mesenchymal stem cells derived from human exocrine pancreas express transcription factors implicated in beta-cell development.
abstract: OBJECTIVE
  Transplantation of in vitro generated islets or insulin-producing cells represents an attractive option to overcome organ shortage. The aim of this study was to isolate, expand, and characterize cells from human exocrine pancreas and analyze their potential to differentiate into beta cells.
  
  
  METHODS
  Fibroblast-like cells growing out of human exocrine tissue were characterized by flow cytometry and by their capacity to differentiate into mesenchymal cell lineages. During cell expansion and after differentiation toward beta cells, expression of transcription factors of endocrine pancreatic progenitors was analyzed by reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Cells emerged from 14/18 human pancreatic exocrine fractions and were expanded up to 40 population doublings. These cells displayed surface antigens similar to mesenchymal stem cells from bone marrow. A culture of these cells in adipogenic and chondrogenic differentiation media allowed differentiation into adipocyte- and chondrocyte-like cells. During expansion, cells expressed transcription factors implicated in islet development such as Isl1, Nkx2.2, Nkx6.1, nestin, Ngn3, Pdx1, and NeuroD. Activin A and hepatocyte growth factor induced an expression of insulin, glucagon, and glucokinase.
  
  
  CONCLUSIONS
  Proliferating cells with characteristics of mesenchymal stem cells and endocrine progenitors were isolated from exocrine tissue. Under specific conditions, these cells expressed little insulin. Human pancreatic exocrine tissue might thus be a source of endocrine cell progenitors.
authors.affiliation: Department of Surgery, Surgical Research Unit, University Hospital Geneva, Geneva, Switzerland.
authors.forename: Reto M
authors.initials: RM
authors.lastname: Baertschiger
authors.forename: Domenico
authors.initials: D
authors.lastname: Bosco
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Veronique
authors.initials: V
authors.lastname: Serre-Beinier
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.forename: Leo H
authors.initials: LH
authors.lastname: Buhler
authors.forename: Carmen
authors.initials: C
authors.lastname: Gonelle-Gispert
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009687:Nuclear Proteins; D046790:Pancreas, Exocrine / Q000254:growth & development / Q000378:metabolism*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D007328:Insulin; D007381:Intermediate Filament Proteins; C577484:NES protein, human; C000715631:NKX2-2 protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D009687:Nuclear Proteins; D014157:Transcription Factors; D014746:Vimentin