title: Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells.
abstract: Ductal structures of the adult pancreas contain stem cells that differentiate into islets of Langerhans. Here, we grew pancreatic ductal epithelial cells isolated from prediabetic adult non-obese diabetic mice in long-term cultures, where they were induced to produce functioning islets containing alpha, beta and delta cells. These in vitro-generated islets showed temporal changes in mRNA transcripts for islet cell-associated differentiation markers, responded in vitro to glucose challenge, and reversed insulin-dependent diabetes after being implanted into diabetic non-obese diabetic mice. The ability to control growth and differentiation of islet stem cells provides an abundant islet source for beta-cell reconstitution in type I diabetes.
authors.affiliation: Ixion Biotechnology, 13709 Progress Blvd., Box 13, Alachua, Florida 32615, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Ramiya
authors.forename: M
authors.initials: M
authors.lastname: Maraist
authors.forename: K E
authors.initials: KE
authors.lastname: Arfors
authors.forename: D A
authors.initials: DA
authors.lastname: Schatz
authors.forename: A B
authors.initials: AB
authors.lastname: Peck
authors.forename: J G
authors.initials: JG
authors.lastname: Cornelius
mesh_terms: D000818:Animals; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D007515:Islets of Langerhans / Q000098:blood supply / Q000166:cytology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D018919:Neovascularization, Physiologic; D010183:Pancreatic Ducts / Q000166:cytology* / Q000473:pathology; D011236:Prediabetic State / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*