title: In vitro-generation of islets in long-term cultures of pluripotent stem cells from adult mouse pancreas.
abstract: Pancreatic islets of Langerhans exhibit an architecture and cellular organization ideal for rapid, yet finely controlled, responses to changes in blood glucose levels. In type I, insulin-dependent diabetes (IDD), this organization is lost as a result of the progressive autoimmune response which selectively destroys the insulin-producing pancreatic beta cells. Since beta cells are perceived as end-stage differentiated cells having limited capacity for regeneration in situ, individuals with IDD resulting from beta cell loss or dysfunction require life-long insulin therapy. Efforts to produce islet neogenesis or initiate islet growth in vitro from either fetal or adult tissue have had minimal success. We now report that pancreatic-derived, pluripotent islet-producing stem cells (IPSCs), isolated from prediabetic mice, can be grown in long-term cultures and differentiated into immature functional islet-like structures containing cells which express low levels of insulin, glucagon and/or somatostatin. When such in vitro grown islets were implanted into clinically diabetic NOD mice, the implanted mice were successfully weaned from insulin long-term (>50 days) without ill effects. The implanted mice maintained blood glucose levels just above euglycemic (180-220 mg/dl) and showed no signs of disease. Thus, this technical breakthrough provides new therapeutic approaches to diabetes as an alternative to insulin therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Gainesville 32610, U.S.A.
authors.forename: J G
authors.initials: JG
authors.lastname: Cornelius
authors.forename: V
authors.initials: V
authors.lastname: Tchernev
authors.forename: K J
authors.initials: KJ
authors.lastname: Kao
authors.forename: A B
authors.initials: AB
authors.lastname: Peck
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers; D006728:Hormones / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D008855:Microscopy, Electron, Scanning; D016376:Oligonucleotides, Antisense; D010179:Pancreas / Q000166:cytology*; D010187:Pancreatic Hormones / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
chemical_list: D017931:DNA Primers; D006728:Hormones; D016376:Oligonucleotides, Antisense; D010187:Pancreatic Hormones; D012333:RNA, Messenger