title: Generation of stem cell-derived β-cells from patients with type 1 diabetes.
abstract: We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past. These T1D SC-β cells express β-cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of β-cell stress. Using these assays, we find no major differences in T1D SC-β cells compared with SC-β cells derived from non-diabetic patients. These results show that T1D SC-β cells could potentially be used for the treatment of diabetes, drug screening and the study of β-cell biology.
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, Campus Box 8127, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.|Department of Biomedical Engineering, Washington University in St Louis, 1 Brookings Drive, St Louis, Missouri 63130, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Millman
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Xie
authors.affiliation: Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Alana
authors.initials: A
authors.lastname: Van Dervort
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
authors.forename: Mads
authors.initials: M
authors.lastname: Gürtler
authors.affiliation: Semma Therapeutics, Inc. 450 Kendall Street, Suite 2B Cambridge, Massachusetts 02142, USA.
authors.forename: Felicia W
authors.initials: FW
authors.lastname: Pagliuca
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D007328:Insulin; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D033581:Stem Cell Transplantation
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin