title: Maturation of stem cell-derived beta-cells guided by the expression of urocortin 3.
abstract: Type 1 diabetes (T1D) is a devastating disease precipitated by an autoimmune response directed at the insulin-producing beta-cells of the pancreas for which no cure exists. Stem cell-derived beta-cells show great promise for a cure as they have the potential to supply unlimited numbers of cells that could be derived from a patient's own cells, thus eliminating the need for immunosuppression. Current in vitro protocols for the differentiation of stem cell-derived beta-cells can successfully generate pancreatic endoderm cells. In diabetic rodents, such cells can differentiate further along the beta-cell lineage until they are eventually capable of restoring normoglycemia. While these observations demonstrate that stem cell-derived pancreatic endoderm has the potential to differentiate into mature, glucose-responsive beta-cells, the signals that direct differentiation and maturation from pancreatic endoderm onwards remain poorly understood. In this review, we analyze the sequence of events that culminates in the formation of beta-cells during embryonic development. and summarize how current protocols to generate beta-cells have sought to capitalize on this ontogenic template. We place particular emphasis on the current challenges and opportunities which occur in the later stages of beta-cell differentiation and maturation of transplantable stem cell-derived beta-cells. Another focus is on the question how the use of recently identified maturation markers such as urocortin 3 can be instrumental in guiding these efforts.
authors.affiliation: The Salk Institute for Biological Studies, Clayton Laboratories for Peptide Biology, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Talitha
authors.initials: T
authors.lastname: van der Meulen
authors.affiliation: The Salk Institute for Biological Studies, Clayton Laboratories for Peptide Biology, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Huising
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D038081:Organogenesis; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D054832:Urocortins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C426704:UCN3 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone