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

Abstract

ObjectTo 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 MethodsAfter being incubated with and without CSPIO (10 µg/ml), C57BL/6 mouse islets were examined under transmission electron microscope (TEM) and their insulin secretion was measured. Cytotoxicity was examined in α (αTC1) and β (NIT-1 and βTC) 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.ResultsAfter incubation of mouse islets with CSPIO (10 µg/mL), TEM showed CSPIO in endocytotic vesicles of α- and β-cells at 8 h. Incubation with CSPIO did not affect insulin secretion from islets and death rates of αTC1, NIT-1 and βTC 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.ConclusionOur results indicate that after syngeneic and allogeneic transplantation, islets labeled with CSPIO nanoparticles can be effectively and safely imaged by MR.

Enabling non-invasive assessment of an engineered endothelium on ePTFE vascular grafts without increasing oxidative stress

“…For example, Juan et al used chitosan-coated SPIONs to label mouse islets and imaged them for up to 5 weeks after implanting them in the animal. [40] Thu et al used iron oxide-labeled therapeutic neural stem cells to visualize the cells in a brain tumor model. [41] It is more challenging to use MRI to visualize a single layer of cells, due to the limited spatial resolution of MRI, which is in the order of hundreds of microns, and the cytotoxicity issues observed by us and others.…”

Stem Cell Imaging: Tools to Improve Cell Delivery and Viability

“…But the coated SPION can stably exist in cells. Labeling cells with dextran-coated SPION [ 42 ], chitosan [ 43 ], polyethylene glycol (PEG 2K) [ 44 ], and alkyl-polycation [ 45 ] at 30 μ g/mL, 80 μ g/mL, 100 μ g/mL iron of SPION, and 7 μ g Fe/mL, respectively, shows negligible cytotoxic effects and clear MR signal detection. Ultimately, every label has to be studied because even slight differences can cause major changes in toxicity profiles.…”

Three-dimensional islet graft histology: panoramic imaging of neural plasticity in sympathetic reinnervation of transplanted islets under the kidney capsule

“…Male inbred C57BL/6 mice, age 8 -12 wk, were used as donors and recipients for transplantation (17)(18)(19)24). The recipients were diabetic or normoglycemic.…”