title: Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells.
abstract: Embryonic stem (ES) cells have been proposed to be a powerful tool in the study of pancreatic disease, as well as a potential source for cell replacement therapy in the treatment of diabetes. However, data demonstrating the feasibility of using pancreatic islet-like cells differentiated from ES cells remain controversial. In this study we characterized ES cell-derived insulin-expressing cells and assessed their suitability for the treatment of type I diabetes. ES cell-derived insulin-stained cell clusters expressed insulin mRNA and transcription factors associated with pancreatic development. The majority of insulin-positive cells in the clusters also showed immunoreactivity for C-peptide. Insulin was stored in the cytoplasm and released into the culture medium in a glucose-dependent manner. When the cultured cells were transplanted into diabetic mice, they reversed the hyperglycemic state for approximately 3 weeks, but the rescue failed due to immature teratoma formation. Our studies demonstrate that reversal of hyperglycemia by transplantation of ES cell-derived insulin-producing cells is possible. However, the risk of teratoma formation would need to be eliminated before ES cell-based therapies for the treatment of diabetes are considered.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Seh-Hoon
authors.initials: SH
authors.lastname: Oh
authors.forename: Liya
authors.initials: L
authors.lastname: Pi
authors.forename: Heather M
authors.initials: HM
authors.lastname: Hatch
authors.forename: Tom
authors.initials: T
authors.lastname: Shupe
authors.forename: Bryon E
authors.initials: BE
authors.lastname: Petersen
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D007150:Immunohistochemistry; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000166:cytology; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013724:Teratoma / Q000209:etiology*
chemical_list: D007328:Insulin; D012333:RNA, Messenger