title: Isolated human islets contain a distinct population of mesenchymal stem cells.
abstract: Islet replacement is a promising approach for type-1 diabetes treatment, but the shortage of organ donors demands new sources of β-cells. The use of stem/precursor cells may represent an attractive alternative. Islet-derived stem/precursor cells (hIPC) have been isolated from human islet preparations, but neither their origin, nor their contribution to β-cell formation in the adult pancreas, are well understood. To study these cells in more detail hIPC were isolated from purified human islets, cultured and functionally characterized. Cultured hIPC did not express the genes for endocrine hormones. These cells exhibited the capacity to aggregate and form clusters when transferred to serum-free medium. In these clusters the expression of insulin, glucagon, and somatostatin genes is induced. Human IPC lack expression of Von Willebrand Factor, CD31, CD34, CD45, and CK19 and CA19.9, demonstrating that hIPC are neither of hematopoietic, endothelial, nor of ductal origin. The mesenchymal stem cells (MSC) markers CD105, CD90, CD73, CD44, CD29, and CD13 are expressed, as well as nestin and vimentin. With the appropriate stimuli the cells can differentiate into adipocytes and osteoblasts lineages. Also hIPC express the pericyte markers CD146, NG2, αSMA and PDGF-Rβ. Immunoflowcytometry revealed that human islets contain 2.0 ± 0.8% of CD105/CD90 double-positive cells. Confocal microscopy showed that these cells reside within the human islets. Altogether our data revealed the presence of a distinct MSC-like stem cell population in isolated human islets.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. f.carlotti@lumc.nl
authors.forename: Françoise
authors.initials: F
authors.lastname: Carlotti
authors.forename: Arnaud
authors.initials: A
authors.lastname: Zaldumbide
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Loomans
authors.forename: Evelien
authors.initials: E
authors.lastname: van Rossenberg
authors.forename: Marten
authors.initials: M
authors.lastname: Engelse
authors.forename: Eelco J
authors.initials: EJ
authors.lastname: de Koning
authors.forename: Rob C
authors.initials: RC
authors.lastname: Hoeben
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D000071063:Endoglin; D005934:Glucagon / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D018800:Thy-1 Antigens; D013004:Somatostatin; D005934:Glucagon