Magnetic Iron Oxide Nanoparticle Labeling of Photoreceptor Precursors for Magnetic Resonance Imaging

Abstract

In vivo

cell tracking is a powerful tool for the optimization and monitoring of cell therapy. Magnetic resonance imaging (MRI) can be used to visualize transplanted cells labeled with superparamagnetic iron oxide nanoparticles (SPIONs), as well as the surrounding tissues. However, the applicability of these techniques in vivo in the retina has not been investigated. The goal of this study was to evaluate the feasibility of SPION labeling and MRI tracking of photoreceptor precursors transplanted into the subretinal space. Photoreceptor precursors derived from human embryonic stem cells were labeled with SPIONs using the FeraTrack MRI contrast agent kit (Miltenyi Biotec, Inc., Auburn, CA). The proliferation, viability, and differentiation capacity of SPION-labeled photoreceptor precursors were assessed in vitro and were found to be unaffected by SPION labeling. Royal College of Surgeons rats were classified into four experimental groups as follows: those injected with culture medium, unlabeled photoreceptor precursors, SPION-containing medium, and SPION-labeled photoreceptor precursors. All rats underwent subretinal injection by a transscleral approach and were examined by 9.4T MRI with T2*-weighted sequences (T2*WI) from 1 day to 12 weeks after transplantation. Hypointense signals corresponding to the transplanted SPION-labeled photoreceptor precursors and SPION-containing medium were clearly visible at the injection site at 1 day after transplantation. In contrast, no hypointense signal was observed in rats injected with culture medium or unlabeled photoreceptor precursors. The hypointense signal of the SPION-labeled photoreceptor precursors decreased, but remained visible over the entire follow-up period. At 12 weeks after transplantation, histological analysis showed that transplanted SPION-labeled photoreceptor precursors were viable, and their distribution corresponded to the hypointense signal observed on T2*WI. However, the hypointense signal of the SPION-containing medium markedly decreased over time until it was undetectable at 12 weeks after transplantation. This study demonstrated that SPION labeling and MRI tracking of photoreceptor precursors transplanted into the subretinal space are feasible and can be utilized in cell therapy for degenerative retinal diseases.

Impact Statement

This study describes the methods and results of superparamagnetic iron oxide nanoparticle (SPION) labeling and magnetic resonance imaging (MRI) tracking of human embryonic stem cell-derived photoreceptor precursors transplanted into the subretinal space of Royal College of Surgeons rats. SPION labeling and MRI tracking provide information about the biodistribution of transplanted photoreceptor precursors, which is necessary for improving the functional benefits of cell therapy for degenerative retinal diseases.