Novel immunological strategies for islet transplantation

Pharmacol Res. 2015 Aug;98:69-75. doi: 10.1016/j.phrs.2014.06.016. Epub 2014 Jul 8.

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.

Keywords: Costimulatory molecules; Encapsulation; Immune-therapies; Immunosuppression; Islet transplantation; Type 1 diabetes; Xenograft.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1 / therapy
  • Heterografts
  • Humans
  • Immunosuppression Therapy / methods*
  • Immunosuppressive Agents / therapeutic use*
  • Islets of Langerhans Transplantation / immunology*
  • Islets of Langerhans Transplantation / methods*
  • Swine
  • Transplantation, Autologous

Substances

  • Immunosuppressive Agents