Injectable alginate hydrogels improve the effects of subretinal hiPSC-derived RPE cell therapy on retinal degeneration in rats

Subretinal delivery of retinal pigment epithelium (RPE) cells is an important treatment for retinal degeneration patients, and the cell suspension method is the most common approach. Injectable hydrogel-mediated cell engraftment is expected to potentially improve cell transplantation outcomes. Here, alginate hydrogels were used to deliver human-induced pluripotent stem cell (hiPSC)-differentiated RPE cells or an RPE cell line (ARPE-19 cells) into the subretinal sites of Royal College of Surgeons (RCS) rats with retinal degeneration. RPE cell-grafted sites were monitored operating a retinal imaging instrument, and the visual functions of RCS rats were assessed via optomotor response (OMR) and electroretinogram (ERG), and retinal structure was analyzed histologically. The OMR results revealed similar spatial vision recovery among the cell transplantation groups injected with and without hydrogels. However, the ERG results revealed superior light perception in RCS rats treated with hydrogel-mediated RPE cell transplantation, particularly compared to hiPSC-derived RPE cell transplantation. This is because OMR evaluates movement of RCS rat eyes, which is difficult to evaluate visual acuity precisely. Optical coherence tomography at four and eight weeks post-transplantation confirmed long-term RPE cell retention and a thickened outer nuclear layer at injection sites after RPE cell engraftment with injectable hydrogels but not without injectable hydrogels; this was supported by the histological results showing retinal outer nuclear layer preservation for 8 weeks. These findings indicate that compared with RPE cell suspensions, alginate hydrogels enhance RPE cell transplantation outcomes and that the structural and functional rescue effects of hiPSC-derived RPE cells with injectable hydrogels are valuable. Hydrogel-mediated delivery represents a promising strategy for improving subretinal cell transplantation efficacy.