The graft survival protection of subcutaneous allogeneic islets with hydrogel grafting and encapsulated by CTLA4Ig and IL1ra

In this study, we examined the combined effect of two recombinant immunomodulator proteins, cytotoxic T-lymphocyte antigen-4-Ig (CTLA4Ig) and interleukin-1 receptor antagonist (IL1ra), on the survival of subcutaneous mouse islet grafts with temperature-sensitive hydrogel, poly(N-isopropylacrylamide) (pNIPAAm)-chitosan-hyaluronic acid (CPNHA), and gelatin microspheres in an allogeneic mouse model. The phase-transition temperature for the CTLA4Ig-grafted CPNHA (CPNCHA) was 28 °C. An in vitro cytotoxicity assay and in vivo tissue reactions showed that both CPNCHA and the gelatin microspheres were biocompatible, biodegradable and nontoxic. The survival of the allogeneic islets was prolonged when the grafts were transplanted into a subcutaneous matrix composed of CPNCHA and gelatin microspheres containing IL1ra relative to those implanted in CPNHA containing gelatin microspheres without an immunomodulator. In conclusion, our results suggest that the temperature-sensitive hydrogel, CPNCHA, is a suitable subcutaneous matrix for islet transplantation, and grafted CTLA4Ig and encapsulated IL1ra reduce immune rejection and prolong the survival of the functioning allogeneic islets.