Clinical islet transplantation has demonstrated success in treating T1D. One current limitation is the traditional transplant site, which can be prone to mechanical stress and inflammation. Transplantation of pancreatic islets into alternative sites is preferable, but challenging, as it may require a three-dimensional structure for mechanical protection and to confine islets to a well-defined, retrievable space where blood vessel growth can occur. The authors have fabricated a stable and porous structure from synthetic materials and investigated islet retention and distribution, metabolic function, and glucose-dependent insulin secretion within these materials. Islets from multiple sources, including rodents, nonhuman primates, and humans, were tested in the lab. They observed a high degree of islet retention and distribution within the structure. Islets loaded within these synthetic structures exhibited viability and function comparable to standard culture conditions when incubated under normal oxygen conditions, but displayed improved viability compared to standard culture controls under low oxygen conditions. The benefit of these synthetic structures to support islet function was evaluated after transplantation into diabetic rats, which promptly achieved normal glycemic control. Collectively, these results are promising in that they indicate the potential value of such synthetic structures for maintaining functioning islets following transplantation into a clinically relevant site that provides spatial distribution of islets, as well as needed blood flow for improved survival.
Ramifications for Individuals with T1D:
The implantation of functioning beta cells using an encapsulation strategy to establish insulin independence must overcome multiple technical challenges. The synthetic structure tested in this research may be an important component of success in future beta cell encapsulation products.
This study was funded in part by JDRF.
Investigators and Institutions:
This work was conducted by Dr. Camillo Ricordi and his colleagues at the University of Miami, Diabetes Research Institute.
Pedraza E, Brady AC, Fraker CA, Molano RD, Sukert S, Berman DM, Kenyon NS, Pileggi A, Ricordi C, Stabler CL. (2012) Macroporous Three Dimensional PDMS Scaffolds for Extrahepatic Islet Transplantation. Cell Transplant. 2012 Oct 2. [Epub ahead of print]