In Vivo Cell Tracking After Subretinal Transplantation Using Magnetic Iron Oxide Labeling and Magnetic Resonance Imaging
Year: 2020
Type: dissertation
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 cells which were transplanted into the subretinal space. Neuro-progenitor (NP) cells and photoreceptor precursors derived from human embryonic stem cells were labeled with SPIONs using the FeraTrack MRI contrast agent kit. SPION-labeled NP cells which were transplanted in the subretinal space of Brown-Norway rats were visualized with T2*-weighted sequences (T2*WI) MRI as hypointense signals for up to 20 weeks. 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 (RCS) 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 RCS rats underwent subretinal injection by a trans-scleral approach and were examined by MRI with 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. In addition, the SPION-labeled photoreceptor precursors showed similar therapeutic effect in RCS rats compared to the unlabeled photoreceptor precursors. This study demonstrated that the SPION labeling and MRI tracking of cells transplanted into the subretinal space is feasible and can be utilized in cell therapy for degenerative retinal diseases.
Author: 마대중
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3034386676