Replacing defective retinal pigment epithelial (RPE) cells with those derived from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) is a potential strategy for treating retinal degenerative diseases. Early clinical trials have demonstrated that hESC-derived or hiPSC-derived RPE cells can be delivered safely as a suspension to the human eye. The next step is transplantation of hESC/hiPSC-derived RPE cells as cell sheets that are more physiological. We have developed a tissue-engineered product consisting of hESC-derived RPE cells grown as sheets on human amniotic membrane as a biocompatible substrate. We established a surgical approach to engraft this tissue-engineered product into the subretinal space of the eyes of rats with photoreceptor cell loss. We show that transplantation of the hESC-RPE cell sheets grown on a human amniotic membrane scaffold resulted in rescue of photoreceptor cell death and improved visual acuity in rats with retinal degeneration compared to hESC-RPE cells injected as a cell suspension. These results suggest that tissue-engineered hESC-RPE cell sheets produced under good manufacturing practice conditions may be a useful approach for treating diseases of retinal degeneration.

用源自人类胚胎干细胞（hESCs）或人类诱导的多能干细胞（hiPSC）的细胞替代有缺陷的视网膜色素上皮（RPE）细胞是治疗视网膜退行性疾病的潜在策略。早期的临床试验表明，hESC来源或hiPSC来源的RPE细胞可以作为悬浮液安全地递送到人眼。下一步是将hESC / hiPSC衍生的RPE细胞作为更具生理性的细胞片进行移植。我们开发了一种组织工程产品，该产品由hESC衍生的RPE细胞组成，在人体羊膜上以薄片形式生长，作为生物相容性基质。我们建立了一种手术方法，将这种组织工程产品植入患有感光细胞丢失的大鼠眼睛的视网膜下间隙。我们显示，与以细胞悬液注射的hESC-RPE细胞相比，在人羊膜支架上生长的hESC-RPE细胞表的移植导致视网膜细胞变性大鼠的光感受器细胞死亡抢救和视敏度的提高。这些结果表明，在良好的生产实践条件下生产的组织工程化的hESC-RPE细胞片可能是治疗视网膜变性疾病的有用方法。