title: Heterogenous expression of nestin in human pancreatic tissue precludes its use as an islet precursor marker.
abstract: The discovery of a pancreatic adult stem cell would have significant implications for cell-based replacement therapies for type 1 diabetes mellitus. Nestin, a marker for neural precursor cells, has been suggested as a possible marker for islet progenitor cells. We have characterized the expression and localization of nestin in both the intact human pancreas and clinical human pancreatic islet grafts. Nestin was found to be expressed at different levels in the acinar component of human pancreatic biopsies depending on donor, as well as in ductal structures and islets to some degree. In islets, insulin-producing beta-cells rarely co-expressed the protein, and in the ducts a small percentage (1-2%) of cells co-expressed nestin and cytokeratin 19 (CK19) while most expressed only CK19 (90%) or nestin (5-10%) alone. Assessment of nestin expression in neonatal pancreatic sections revealed an increased number of islet-associated positive cells as compared with adult islets. Nestin immunoreactivity was also found in cells of the pancreatic vasculature and mesenchyme as evidenced by co-localization with smooth muscle actin and vimentin. Samples from post-islet isolation clinical islet grafts revealed a pronounced heterogeneity in the proportion of nestin-positive cells (<1-72%). Co-localization studies in these grafts showed that nestin is not co-expressed in endocrine cells and rarely (<5%) with cytokeratin-positive ductal cells. However, relatively high levels of co-expression were found with acinar cells and cells expressing the mesenchymal marker vimentin. In conclusion we have shown a diffuse and variable expression of nestin in human pancreas that may be due to a number of different processes, including post-mortem tissue remodeling and cellular differentiation. For this reason nestin may not be a suitable marker solely for the identification of endocrine precursor cells in the pancreas.
authors.affiliation: Surgical Medical Research Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
authors.forename: C N
authors.initials: CN
authors.lastname: Street
authors.forename: J R T
authors.initials: JR
authors.lastname: Lakey
authors.forename: K
authors.initials: K
authors.lastname: Seeberger
authors.forename: L
authors.initials: L
authors.lastname: Helms
authors.forename: R V
authors.initials: RV
authors.lastname: Rajotte
authors.forename: A M J
authors.initials: AM
authors.lastname: Shapiro
authors.forename: G S
authors.initials: GS
authors.lastname: Korbutt
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000235:genetics*; D007515:Islets of Langerhans / Q000737:chemistry; D007633:Keratins / Q000032:analysis; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins; D064231:Nestin; D010179:Pancreas / Q000737:chemistry*; D010183:Pancreatic Ducts / Q000737:chemistry; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis*; D014746:Vimentin / Q000032:analysis
chemical_list: D015415:Biomarkers; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D012333:RNA, Messenger; D014746:Vimentin; D007633:Keratins