Islet Trasplantation Program (ITP)

Heads: Lorenzo Piemonti and Paola Maffi

Vision

The mission of this program is to achieve long-lasting insulin independence in patients with type 1 diabetes (T1D) undergoing portal vein islet transplantation. Recognized experts in islet transplantation, immunological tolerance, liver immunopathology and non-invasive imaging have been brought together to address and modify innate and adaptive immune responses to islet transplants that together prevent lifelong persistence of functional islets within the liver.

Goals

Aims of this program are:

  1. to improve donor management, donor selection criteria, organ recovery techniques and islet cell processing techniques. Expected results: identification of more efficient islet cell processing to maximize islet recovery;
  2. to identify and standardize methods for the evaluation of islet preparations intended for transplantation in humans (i.e. cell composition, cell viability, insulin secretion). Expected results: identification and validation of predictor for islet engraftment and post transplant function;
  3. to identify strategies and drugs able to improve islet “engraftment”. Expected results: achieve successful islet transplantation from one donor to one recipient;
  4. to develop single or multi centre clinical trial to test new immunosuppression and tolerogenic strategies. Expected results: achieve successful islet transplantation without immunosuppression or with less toxic immunosuppressive regimens;
  5. to provide islets for researchers. Expected results: support research activity related to β cell biology in Europe.

Main achievements (updated 2012)

During the last year we:

  • demonstrated that inhibition of CXCR2 is crucial for improving islet engraftment and survival. On this basis a phase 2 clinical trial (NCT01220856) was published testing CXCR2 inhibitor in association with the conventional immunosuppressive therapy;
  • started a phase 3, multicenter, randomized, double-blind, parallel assignment study to assess the efficacy and safety of the CXCR1/2 inhibitor reparixin in pancreatic islet transplantation (NCT01817959);
  • extended the clinical indication of islet autotransplantation to a broader population of patients undergoing pancreatic surgery including subjects with technically unfeasible or high risk pancreatic anastomosis during partial pancreatectomy and subjects undergoing completion pancreatectomy because of anastomosis leakage after pancreatoduodenectomy for nonmalignant or malignant diseases (NCT01702051);
  • started a phase 2 study to compare bone marrow vs. liver as site for islet transplantation in patients with type 1 diabetes (NCT01722682);
  • coordinate the European Consortium for Islet Transplantation supporting the research activity related to β cell biology in Europe.