The effects of 8-arm-PEG-catechol/heparin shielding system and immunosuppressive drug, FK506 on the survival of intraportally allotransplanted islets

Abstract

This study proposed a double-layer shielding method of using 8-arm-PEG-catechol (PEG(8)) and N-hydroxysuccinimidyl-linked unfractionated heparin (UFH-NHS) for the prevention of instant blood-mediated inflammatory reaction (IBMIR) and immune reactions against transplanted pancreatic islets. The surface of islet was evenly covered by PEG(8) and UFH-NHS. Both viability and functionality of islets were evaluated in vitro, and the anti-coagulation effect of conjugated heparin on the islet surface was also evaluated. The inhibition effects of PEG(8)/UFH double-layer shielding system on immune reactions and IBMIR induced by transplanted islets were evaluated in an allograft model. When pancreatic islets of Sprague Dawley (SD) rats were transplanted in the liver of F344 rats, the mean survival time (MST) of PEG(8)/UFH double-layer shielded islets (6.8 +/- 1.6 days) was statistically increased, compared to that of unmodified islets (3.6 +/- 1.1 days). Furthermore, when 0.5 mg/kg of FK506 was daily administered, the MST of double-layer shielded islet (15.0 +/- 2.1 days) was increased by two-fold, compared to that of unmodified islets treated with the same dose of FK506 (8.0 +/- 2.4 days). Therefore, a newly developed strategy of combining the PEG(8)/UFH double-layer shielding system with FK506 would certainly be effective for preventing immune activation and IBMIR against allotransplanted islets.