Synergistic Effect of Surface Modification With Poly(ethylene glycol) and Immunosuppressants on Repetitive Pancreatic Islet Transplantation Into Antecedently Sensitized Rat

Abstract

Background. Polymeric modification of islet surface is highly effective in preventing transplanted islets against host immune reactions. However, grafted islets are eventually rejected by the host immune reaction. Thus, repetitive islet transplantation is needed to treat type 1 diabetic patients experiencing graft rejection. We explored whether using poly(ethylene glycol) (PEG) as surface camouflage of islets (PEGylation) can be an affordable immunoprotective remedy for repeated islet transplantation. Methods. The surface coverage of PEG was evaluated in vitro. The viability of PEGylated islets cocultured with sensitized or nonsensitized splenocytes was evaluated using lactate dehydrogenase assay. In addition, the effect of surface modification on immunoprotection for repetitively transplanted islets was evaluated in a sensitized rat model. Results. Unmodified islets transplanted in combination with Cyclosporine (CsA) and anti-CD4 monoclonal antibody (OX-38) into the sensitized recipients did not maintain a normal level of blood glucose over 20 days. Interestingly, however, three of the five recipients became normoglycemic up to 30 days when PEGylated islets were transplanted in combination with CsA and OX-38. Conclusion. These results demonstrated that PEGylation alone was not an affordable immunoprotective method, but the combination of CsA and OX-38 along with PEGylation showed a highly improved a synergic effects on the inhibition of sensitized host immune reactions.