title: Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells.
abstract: Transplantation of pancreatic progenitors or insulin-secreting cells derived from human embryonic stem cells (hESCs) has been proposed as a therapy for diabetes. We describe a seven-stage protocol that efficiently converts hESCs into insulin-producing cells. Stage (S) 7 cells expressed key markers of mature pancreatic beta cells, including MAFA, and displayed glucose-stimulated insulin secretion similar to that of human islets during static incubations in vitro. Additional characterization using single-cell imaging and dynamic glucose stimulation assays revealed similarities but also notable differences between S7 insulin-secreting cells and primary human beta cells. Nevertheless, S7 cells rapidly reversed diabetes in mice within 40 days, roughly four times faster than pancreatic progenitors. Therefore, although S7 cells are not fully equivalent to mature beta cells, their capacity for glucose-responsive insulin secretion and rapid reversal of diabetes in vivo makes them a promising alternative to pancreatic progenitor cells or cadaveric islets for the treatment of diabetes.
authors.affiliation: BetaLogics Venture, Janssen R&D LLC, Raritan, New Jersey, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Rezania
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Bruin
authors.affiliation: BetaLogics Venture, Janssen R&D LLC, Raritan, New Jersey, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Arora
authors.affiliation: BetaLogics Venture, Janssen R&D LLC, Raritan, New Jersey, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Rubin
authors.affiliation: BetaLogics Venture, Janssen R&D LLC, Raritan, New Jersey, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Batushansky
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Asadi
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: O'Dwyer
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nina
authors.initials: N
authors.lastname: Quiskamp
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Majid
authors.initials: M
authors.lastname: Mojibian
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tobias
authors.initials: T
authors.lastname: Albrecht
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yu Hsuan Carol
authors.initials: YH
authors.lastname: Yang
authors.affiliation: 1] Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. [2] Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: James D
authors.identifier: 0000000275239433
authors.initials: JD
authors.lastname: Johnson
authors.affiliation: 1] Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. [2] Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D003920:Diabetes Mellitus / Q000473:pathology / Q000628:therapy*; D053595:Embryonic Stem Cells / Q000637:transplantation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000637:transplantation; D051379:Mice; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000637:transplantation*
chemical_list: D007328:Insulin; D005947:Glucose