Novel explant model for human retinal progenitor cell transplantation

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, have led to vision loss for millions worldwide. While stem/progenitor cell transplantation shows promise, its clinical application is limited by poor survival, efflux, and low integration of transplanted cells. Biopolymer scaffolds have been explored to improve viability and differentiation, but most in vitro assessments rely on simplified or endpoint analyses that fail to capture dynamic behaviors. Retinal explant models, which preserve tissue architecture and neuronal connections, provide a more physiologically relevant platform. However, conventional explant models are often limited to endpoint analyses and lack real-time monitoring capabilities. Here, we developed a novel explant model for human retinal progenitor cell (hRPC) transplantation using porcine retinal tissue slice, agarose hydrogel, and confocal microscope with an incubation cage. Retinal tissue slices exhibited comparable viability before and after imaging. Alginate-based hydrogels containing hRPCs were injected adjacent to photoreceptor or ganglion cell layer of cross-sectional retinal tissue slices, enabling visualization of the cells' position relative to retinal tissue slice over time. Real-time confocal imaging tracked key cellular behaviors, including migration, attachment, invasion, viability, and apoptosis. Injected hRPCs displayed random movement within the bulk alginate hydrogel and localized attachment or invasion at the hydrogel-tissue interface. Notably, laminin-incorporated alginate hydrogels promoted cell clustering and facilitated deeper invasion into retinal tissue compared with single cells.