Magnetic Resonance Imaging of Mouse Islet Grafts Labeled with Novel Chitosan-Coated Superparamagnetic Iron Oxide Nanoparticles

Abstract

Object: To better understand the fate of islet isografts and allografts, we utilized a magnetic resonance (MR) imaging technique to monitor mouse islets labeled with a novel MR contrast agent, chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles. Materials and Methods: After being incubated with and without CSPIO (10 mu g/ml), C57BL/6 mouse islets were examined under transmission electron microscope (TEM) and their insulin secretion was measured. Cytotoxicity was examined in alpha (alpha TC1) and beta (NIT-1 and beta TC) cell lines as well as islets. C57BL/6 mice were used as donors and inbred C57BL/6 and Balb/c mice were used as recipients of islet transplantation. Three hundred islets were transplanted under the left kidney capsule of each mouse and then MR was performed in the recipients periodically. At the end of study, the islet graft was removed for histology and TEM studies. Results: After incubation of mouse islets with CSPIO (10 mu g/mL), TEM showed CSPIO in endocytotic vesicles of alpha- and beta-cells at 8 h. Incubation with CSPIO did not affect insulin secretion from islets and death rates of alpha TC1, NIT-1 and beta TC cell lines as well as islets. After syngeneic and allogeneic transplantation, grafts of CSPIO-labeled islets were visualized on MR scans as persistent hypointense areas. At 8 weeks after syngeneic transplantation and 31 days after allogeneic transplantation, histology of CSPIO-labeled islet grafts showed colocalized insulin and iron staining in the same areas but the size of allografts decreased with time. TEM with elementary iron mapping demonstrated CSPIO distributed in the cytoplasm of islet cells, which maintained intact ultrastructure. Conclusion: Our results indicate that after syngeneic and allogeneic transplantation, islets labeled with CSPIO nanoparticles can be effectively and safely imaged by MR.