In Vivo Imaging of Immune Rejection in Transplanted Pancreatic Islets

Abstract

1As islet transplantation becomes an acceptable clinical modality for restoring normoglycemia in type 1 diabetic patients, there is a crucial need for noninvasive assessment of the fate of the grafts. In spite of the success of the Edmonton Protocol, a significant graft loss occurs due to immunological and nonimmunological events immediately after transplantation. Allogeneic rejection in graft recipients is one of the major reasons for islet death and graft failure. Therefore, monitoring the islet rejection using reliable noninvasive methods would significantly aid in clinical assessment of graft success. We have previously developed a method to detect transplanted islets noninvasively using magnetic resonance imaging (MRI). For this procedure, human pancreatic islets are labeled with an MRI contrast agent that enables their visualization on magnetic resonance images. In our present study, we not only detected labeled human islets in a preclinical intrahepatic model of human islet transplantation in mice but also showed that islet rejection can be monitored noninvasively and repeatedly in real time by MRI. In addition, in this study, we have adapted, for islet cell labeling, a Food and Drug Administration-approved commercially available contrast agent, Feridex, that is used clinically for liver imaging. We believe that this agent, in combination with our preclinical model of islet transplantation, will facilitate the transition of imaging immune rejection to clinical trials. Diabetes

Assessment of Human Islet Labeling with Clinical Grade Iron Nanoparticles Prior to Transplantation for Graft Monitoring by MRI

“…In the ferumoxide and in no other place. It should finally be mentioned that non-clinical grade MR scanners, with high magnetic fields (1, 11,12,18). The only pilot study performed on iron nanoparticles (17) released by dead islets are too small in size to individually disturb the MRI signal.…”

Fluorine‐19 MRI for visualization and quantification of cell migration in a diabetes model

“…Superparamagnetic iron-oxide (SPIO) nanoparticle contrast agents have been used to track autoreactive T-cell migration (10 -12). In the NOD mouse, islet transplantation and pancreatic inflammation have been visualized in vivo using SPIO agents (13)(14)(15).…”

Advances of Nanotechnology in the Stem Cells Research and Development

“…But in the same situation, lesions of grafted animals were seen as dark hypointense areas. Compared to control rats, the lesions gathering by MSCs in grafted animals become considerably smaller, which suggested a positive effect of the MSCs on lesion repair [55].Moreover, several successful applications of MR tracking can be found in other organs, such as heart [56], liver [57], kidney [58] and pancreatic islets [59]. It is reported that bronchioalveolar stem cells (BASCs) were successfully isolated from the murine lung using magnetic nanoparticle-based surface-enhanced Raman spectroscopic dots (M-SERS Dots) [60].…”