Targeting New Pathways to Reduce Inflammation During Islet Transplantation and Improve Transplant Outcomes

Although long considered a promising treatment option for T1D, pancreatic islet cell transplantation has been hindered by immune system rejection of the transplanted tissue. The identification of pathways that regulate detrimental post-transplant inflammatory events could improve the management and outcome of transplanted patients and provide approaches to improve the success of early generation encapsulation products. This research identified a type of molecule that plays a crucial role in islet survival after transplantation. Pancreatic islets were found to release abundant amounts of these molecules. Blocking these molecules in mice improved the success of islet transplantation. In humans, an inhibitor of these molecules improved clinical outcomes in a randomized, open-label pilot study of patients with T1D given an islet transplant. These findings indicate that these molecules are on a pathway that regulates islet damage and should be a target for further drug development to improve the efficacy of islet transplantation and encapsulation approaches for islet replacement in patients with T1D.

Ramifications for Individuals with T1D:

This study provides new approaches on how to extend the duration of islet/beta cell functionality in beta cell replacement therapies for individuals with T1D.

JDRF Involvement:

This study was funded in part by JDRF.

Investigators and Institutions:

This work was conducted by Dr. Lorenzo Piemonti and his colleagues at San Raffaele Institute.

Reference:

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. (2012) CXCR1/2 inhibition enhances pancreatic islet survival after transplantation. J Clin Invest. 2012 Oct 1;122(10):3647-51 (Epub 2012 Sep 17).