Cell-based regenerative therapy for retinal diseases: challenges and emerging bioengineering strategies

作者：Yasuaki Iwama, Tomohiro Masuda, Ava Maeyama, Kevin Eade, Martin Friedlander, Kohji Nishida, Michiko Mandai · 发表于：Regenerative Therapy · 年份：2025 · DOI：10.1016/j.reth.2025.11.002 · 被引用次数：3 · 研究领域：Retinal Development and Disorders、CRISPR and Genetic Engineering、Neuroscience and Neural Engineering

Cell-based regenerative therapy holds promise for a broad spectrum of retinal diseases characterized by irreversible photoreceptor cell (PRC) loss, including retinitis pigmentosa (RP) and age-related macular degeneration. While gene therapy has delivered landmark successes for selected indications, it does not directly replace lost PRCs and is not well suited for advanced-stages of diseases. In this context, cell-based regenerative approaches-either PRC suspensions or retinal sheets-aim to rebuild the outer retinal circuitry and restore light responses across different retinal diseases. In addition to its relatively high prevalence (1 in 3000-5000 individuals), the PRC-specific degeneration pattern in RP has motivated numerous preclinical studies aimed at clinical application. In this review, we first outline the two major graft modalities-cell suspensions and retinal sheet transplantation-from the perspective of their respective advantages and limitations. Here, we summarize preclinical and clinical evidence for both modalities, highlighting the first-in-human trial of transplantation of human iPSC-derived retinal organoid sheets in late-stage RP, which demonstrated a favorable safety profile and two-year graft survival. We then analyze the challenges that emerged from this first-in-human trial and discuss potential bioengineering and biological solutions. Finally, we consider the prospects of extending these transplantation strategies beyond RP to macular diseases, where PR...