Institutes
Beta cell biology
The Beta Cell Biology Unit aims to create conditions for the expansion and survival of beta cells under native conditions or after transplantation. In principle, the treatment for type-1 diabetes and many cases of type-2 diabetes lies in the possibility of finding a beta cell mass substitute capable of performing two essential functions: assessing blood sugar levels and secreting appropriate levels of insulin in the vascular bed. Currently, the only available clinical therapy capable of restoring beta cell mass in diabetic patients is the allogenic/autologous transplantation of beta cells (somatic cell therapy with pancreas, Langherans islets or beta cell transplantation). Despite advances in recent years, allogenic somatic therapy is still problematic from several points of view (for instance, the need for immunosuppression therapy and, in case of islet transplantation, the need for many donors for a single recipient and the short life of the transplantation).
In previous years we were able to assess the impact of beta-cell changes on immune status of diabetic patients receiving an islet transplantation, the effectiveness of immunotherapies and their ability to control autoimmune and allogeneic responses.
Research activity
To obtain the long-term replacement of the beta cells in patients with diabetes we therefore propose:
- to study alternative sites for islet transplantation,
- to develop new strategies for the survival of islet by modulating/inhibiting inflammation (specifically the chemokine pathways like CCL2 or CXCL8),
- to improve the success of islet transplantation by cotransplantation with feeder cells (using for this purpose mesenchymal stem cells or endothelial cells),
- to determine the mechanisms of immunization and destruction related to islet autoantigens,
- to identify a renewable source of cells to be used for implementing the transplantable beta cell mass, in particular pluripotent stem cells
Dugnani E, Pasquale V, Liberati D, Citro A, Cantarelli E, Pellegrini S, Marra P, Canu T, Balzano G, Scavini M, Esposito A, Doglioni C, Piemonti L. Modeling the iatrogenic pancreatic cancer risk after islet autotransplantation in mouse. Am J Transplant. 2017 Oct;17(10):2720-2727.
Pellegrini S, Sordi V, Bolla AM, Saita D, Ferrarese R, Canducci F, Clementi M, Invernizzi F, Mariani A, Bonfanti R, Barera G, Testoni PA, Doglioni C, Bosi E, Piemonti L. Duodenal mucosa of patients with type 1 diabetes shows distinctive inflammatory profile and microbiota. J Clin Endocrinol Metab. 2017 May 1;102(5):1468-1477.
Balzano G, Maffi P, Nano R, Mercalli A, Melzi R, Aleotti F, Zerbi A, De Cobelli F, Gavazzi F, Magistretti P, Scavini M, Peccatori J, Secchi A, Ciceri F, Del Maschio A, Falconi M, Piemonti L. Autologous islet transplantation in patients requiring pancreatectomy: a broader spectrum of indications beyond chronic pancreatitis. Am J Transplant. 2016 Jun;16(6):1812-26.
Reni M, Dugnani E, Cereda S, Belli C, Balzano G, Nicoletti R, Liberati D, Pasquale V, Scavini M, Maggiora P, Sordi V, Lampasona V, Ceraulo D, Di Terlizzi G, Doglioni C, Falconi M, Piemonti L. (Ir)relevance of metformin treatment in patients with metastatic pancreatic cancer: an open-label, randomized phase II trial. Clin Cancer Res. 2016 Mar 1;22(5):1076-85.
Citro A, Valle A, Cantarelli E, Mercalli A, Pellegrini S, Liberati D, Daffonchio L, Kastsiuchenka O, Ruffini PA, Battaglia M, Allegretti M, Piemonti L. CXCR1/2 inhibition blocks and reverts type 1 diabetes in mice. Diabetes 2015 Apr;64(4):1329-40.
Maffi P, Balzano G, Ponzoni M, Nano R, Sordi V, Melzi R, Mercalli A, Scavini M, Esposito A, Peccatori J, Cantarelli E, Messina C, Bernardi M, Del Maschio A, Staudacher C, Doglioni C, Ciceri F, Secchi A, Piemonti L. Autologous pancreatic islet transplantation in human bone marrow. Diabetes 2013 Oct;62(10):3523-31.
Mercalli A, Calavita I, Dugnani E, Citro A, Cantarelli E, Nano R, Melzi R, Maffi P, Secchi A, Sordi V, Piemonti L. Rapamycin unbalances the polarization of human macrophages to M1. Immunology 2013 Oct;140(2):179-90.
Balzano G, Maffi P, Nano R, Zerbi A, Venturini M, Melzi R, Mercalli A, Magistretti P, Scavini M, Castoldi R, Carvello M, Braga M, Del Maschio A, Secchi A, Staudacher C, Piemonti L. Extending indications for islet autotransplantation in pancreatic surgery. Ann Surg. 2013 Aug;258(2):210-8.
Piemonti L, Everly MJ, Maffi P, Scavini M, Poli F, Nano R, Cardillo M, Melzi R, Mercalli A, Sordi V, Lampasona V, Espadas de Arias A, Scalamogna M, Bosi E, Bonifacio E, Secchi A, Terasaki PI. Alloantibody and autoantibody monitoring predicts islet transplantation outcome in human type 1 diabetes. Diabetes 2013 May;62(5):1656- 64.
Citro A, Cantarelli E, Maffi P, Nano R, Melzi R, Mercalli A, Dugnani E, Sordi V, Magistretti P, Daffonchio L, Ruffini PA, Allegretti M, Secchi A, Bonifacio E, Piemonti L. CXCR1/2 inhibition enhances pancreatic islet survival after transplantation. J Clin Invest. 2012 Oct 1;122(10):3647-51.
