title: Using stem cells to produce insulin.
abstract: BACKGROUND
  Tremendous progress has been made in generating insulin-producing cells from pluripotent stem cells. The best outcome of the refined protocols became apparent in the first clinical trial announced by ViaCyte, based on the implantation of pancreatic progenitors that would further mature into functional insulin-producing cells inside the patient's body.
  
  
  METHODS
  Several groups, including ours, have contributed to improve strategies to generate insulin-producing cells. Of note, the latest results have gained a substantial amount of interest as a method to create a potentially functional and limitless supply of β-cell to revert diabetes mellitus. This review analyzes the accomplishments that have taken place over the last few decades, summarizes the state-of-art methods for β-cell replacement therapies based on the differentiation of embryonic stem cells into glucose-responsive and insulin-producing cells in a dish and discusses alternative approaches to obtain new sources of insulin-producing cells.
  
  
  CONCLUSIONS
  Undoubtedly, recent events preface the beginning of a new era in diabetes therapy. However, in our opinion, a number of significant hurdles still stand in the way of clinical application. We believe that the combination of the private and public sectors will accelerate the process of obtaining the desired safe and functional β-cell surrogates.
authors.affiliation: a 1 CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine , Avda. Americo Vespucio s/n, 41092 Seville, Spain bernat.soria@cabimer.es ; karim.hmadcha@cabimer.es.|b 2 CIBERDEM, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders , 08036 Barcelona, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Soria
authors.affiliation: a 1 CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine , Avda. Americo Vespucio s/n, 41092 Seville, Spain bernat.soria@cabimer.es ; karim.hmadcha@cabimer.es.
authors.forename: Benoit R
authors.initials: BR
authors.lastname: Gauthier
authors.affiliation: a 1 CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine , Avda. Americo Vespucio s/n, 41092 Seville, Spain bernat.soria@cabimer.es ; karim.hmadcha@cabimer.es.|b 2 CIBERDEM, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders , 08036 Barcelona, Spain.
authors.forename: Franz
authors.initials: F
authors.lastname: Martín
authors.affiliation: a 1 CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine , Avda. Americo Vespucio s/n, 41092 Seville, Spain bernat.soria@cabimer.es ; karim.hmadcha@cabimer.es.|b 2 CIBERDEM, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders , 08036 Barcelona, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Tejedo
authors.affiliation: a 1 CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine , Avda. Americo Vespucio s/n, 41092 Seville, Spain bernat.soria@cabimer.es ; karim.hmadcha@cabimer.es.|b 2 CIBERDEM, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders , 08036 Barcelona, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bedoya
authors.affiliation: a 1 CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine , Avda. Americo Vespucio s/n, 41092 Seville, Spain bernat.soria@cabimer.es ; karim.hmadcha@cabimer.es.|b 2 CIBERDEM, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders , 08036 Barcelona, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: Rojas
authors.affiliation: a 1 CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine , Avda. Americo Vespucio s/n, 41092 Seville, Spain bernat.soria@cabimer.es ; karim.hmadcha@cabimer.es.|b 2 CIBERDEM, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders , 08036 Barcelona, Spain.
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Hmadcha
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D003920:Diabetes Mellitus / Q000628:therapy; D053595:Embryonic Stem Cells / Q000166:cytology; D044127:Epigenesis, Genetic; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000637:transplantation; D035683:MicroRNAs / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007328:Insulin; D035683:MicroRNAs
keywords: cell differentiation; diabetes; islet development; pancreatic organogenesis; pluripotent stem cells; β-cell