title: Novel immunological strategies for islet transplantation.
abstract: Islet transplantation has been demonstrated to improve glycometabolic control, to reduce hypoglycemic episodes and to halt the progression of diabetic complications. However, the exhaustion of islet function and the side effects related to chronic immunosuppression limit the spread of this technique. Consequently, new immunoregulatory protocols have been developed, with the aim to avoid the use of a life-time immunosuppression. Several approaches have been tested in preclinical models, and some are now under clinical evaluation. The development of new small molecules and new monoclonal or polyclonal antibodies is continuous and raises the possibility of targeting new costimulatory pathways or depleting particular cell types. The use of stem cells and regulatory T cells is underway to take advantage of their immunological properties and to induce tolerance. Xenograft islet transplantation, although having severe problems in terms of immunological compatibility, could theoretically provide an unlimited source of donors; using pigs carrying human immune antigens has showed indeed promising results. A completely different approach, the use of encapsulated islets, has been developed; synthetic structures are used to hide islet alloantigen from the immune system, thus preserving islet endocrine function. Once one of these strategies is demonstrated safe and effective, it will be possible to establish clinical islet transplantation as a treatment for patients with type 1 diabetes long before the onset of diabetic-related complications.
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Transplant Medicine, IRCCS Ospedale San Raffaele, Milano, Italy; Univerista' degli Studi di Roma "Tor Vergata", Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tezza
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Transplant Medicine, IRCCS Ospedale San Raffaele, Milano, Italy.
authors.forename: Moufida
authors.initials: M
authors.lastname: Ben Nasr
authors.affiliation: Transplant Medicine, IRCCS Ospedale San Raffaele, Milano, Italy; Dompé Inc. Research and Development Department, Diabetes and Transplantation Unit, New York, NY, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vergani
authors.affiliation: Transplant Medicine, IRCCS Ospedale San Raffaele, Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valderrama Vasquez
authors.affiliation: Transplant Medicine, IRCCS Ospedale San Raffaele, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Maestroni
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Abdi
authors.affiliation: Transplant Medicine, IRCCS Ospedale San Raffaele, Milano, Italy; Universita' Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Secchi
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Transplant Medicine, IRCCS Ospedale San Raffaele, Milano, Italy. Electronic address: paolo.fiorina@childrens.harvard.edu.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorina
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D064593:Heterografts; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D013552:Swine; D014182:Transplantation, Autologous
chemical_list: D007166:Immunosuppressive Agents
keywords: Costimulatory molecules; Encapsulation; Immune-therapies; Immunosuppression; Islet transplantation; Type 1 diabetes; Xenograft