title: Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo.
abstract: Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with approximately 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional beta-cells, including expression of critical beta-cell transcription factors, appropriate processing of proinsulin and the presence of mature endocrine secretory granules. Finally, in a test of therapeutic potential, we demonstrate that implantation of hES cell-derived pancreatic endoderm protects against streptozotocin-induced hyperglycemia. Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.
authors.affiliation: Novocell, Inc., 3550 General Atomics Ct., San Diego, California 92121, USA.
authors.forename: Evert
authors.initials: E
authors.lastname: Kroon
authors.forename: Laura A
authors.initials: LA
authors.lastname: Martinson
authors.forename: Kuniko
authors.initials: K
authors.lastname: Kadoya
authors.forename: Anne G
authors.initials: AG
authors.lastname: Bang
authors.forename: Olivia G
authors.initials: OG
authors.lastname: Kelly
authors.forename: Susan
authors.initials: S
authors.lastname: Eliazer
authors.forename: Holly
authors.initials: H
authors.lastname: Young
authors.forename: Mike
authors.initials: M
authors.lastname: Richardson
authors.forename: Nora G
authors.initials: NG
authors.lastname: Smart
authors.forename: Justine
authors.initials: J
authors.lastname: Cunningham
authors.forename: Alan D
authors.initials: AD
authors.lastname: Agulnick
authors.forename: Kevin A
authors.initials: KA
authors.lastname: D'Amour
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Carpenter
authors.forename: Emmanuel E
authors.initials: EE
authors.lastname: Baetge
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000639:trends*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D019397:Pancreas, Artificial / Q000639:trends; D023822:Tissue Engineering / Q000639:trends*
chemical_list: D007328:Insulin; D005947:Glucose