This study defines how The human retina fails to regenerate and cell-based therapies offer options for treatment of blinding retinal diseases, such as macular degeneration and retinitis pigmentosa. The last decade has witnessed remarkable advances in generation of retinal cells and retinal tissue from human pluripotent stem cells (PSCs). The development of 3D culture systems allowing generation of human retinal organoids has substantially increased the access to human material for future clinical applications aiming at replacing the lost photoreceptors in retinal degenerative diseases. This review outlines the advances that have been made toward generation and characterization of transplantable photoreceptors from PSCs and summarizes the current status of PSC-based preclinical studies for photoreceptor replacement conducted in animal models. Considering the recent turning point in our understanding of donor photoreceptor integration, this review focuses on the most crucial obstacles that hinder the photoreceptor replacement, discusses the most promising strategies to overcome them in the future, and provides a perspective on the approaching advancement in the application of PSC technology for treatment of photoreceptor degenerative diseases.

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