title: The state of the art of islet transplantation and cell therapy in type 1 diabetes.
abstract: In patients with type 1 diabetes (T1D), pancreatic β cells are destroyed by a selective autoimmune attack and their replacement with functional insulin-producing cells is the only possible cure for this disease. The field of islet transplantation has evolved significantly from the breakthrough of the Edmonton Protocol in 2000, since significant advances in islet isolation and engraftment, together with improved immunosuppressive strategies, have been reported. The main limitations, however, remain the insufficient supply of human tissue and the need for lifelong immunosuppression therapy. Great effort is then invested in finding innovative sources of insulin-producing β cells. One old alternative with new recent perspectives is the use of non-human donor cells, in particular porcine β cells. Also the field of preexisting β cell expansion has advanced, with the development of new human β cell lines. Yet, large-scale production of human insulin-producing cells from stem cells is the most recent and promising alternative. In particular, the optimization of in vitro strategies to differentiate human embryonic stem cells into mature insulin-secreting β cells has made considerable progress and recently led to the first clinical trial of stem cell treatment for T1D. Finally, the discovery that it is possible to derive human induced pluripotent stem cells from somatic cells has raised the possibility that a sufficient amount of patient-specific β cells can be derived from patients through cell reprogramming and differentiation, suggesting that in the future there might be a cell therapy without immunosuppression.
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pellegrini
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cantarelli
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Sordi
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Nano
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. piemonti.lorenzo@hsr.it.
authors.forename: Lorenzo
authors.identifier: http://orcid.org/0000-0002-2172-2198
authors.initials: L
authors.lastname: Piemonti
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000637:transplantation*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*
keywords: Islet transplantation; Pluripotent stem cells; Xenotransplantation; β Cell replacement