title: The Human Endocrine Pancreas: New Insights on Replacement and Regeneration.
abstract: Islet transplantation is an effective cell therapy for type 1 diabetes (T1D) but its clinical application is limited due to shortage of donors. After a decade-long period of exploration of potential alternative cell sources, the field has only recently zeroed in on two of them as the most likely to replace islets. These are pluripotent stem cells (PSCs) (through directed differentiation) and pancreatic non-endocrine cells (through directed differentiation or reprogramming). Here we review progress in both areas, including the initiation of Phase I/II clinical trials using human embryonic stem cell (hESc)-derived progenitors, advances in hESc differentiation in vitro, novel insights on the developmental plasticity of the pancreas, and groundbreaking new approaches to induce β cell conversion from the non-endocrine compartment without genetic manipulation.
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: jdominguez2@med.miami.edu.
authors.forename: Juan
authors.initials: J
authors.lastname: Domínguez-Bendala
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lanzoni
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Klein
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Álvarez-Cubela
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: rpastori@med.miami.edu.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Pastori
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology / Q000637:transplantation; D000818:Animals; D002454:Cell Differentiation; D000066670:Cell Plasticity; D000067470:Cellular Reprogramming Techniques / Q000639:trends; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology / Q000637:transplantation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology / Q000637:transplantation; D007515:Islets of Langerhans / Q000166:cytology / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000639:trends; D008954:Models, Biological
keywords: diabetes; human embryonic stem cells; islets; pancreatic regeneration; β cells