Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A(∗)STAR), Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Eye Research Institute (SERI), Singapore, Singapore.
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A(∗)STAR), Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Stem Cell Reports. 2021 Feb 9;16(2):237-251. doi: 10.1016/j.stemcr.2020.12.007. Epub 2021 Jan 14.
Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.
最近,视网膜色素上皮 (RPE) 移植治疗年龄相关性黄斑变性等疾病的临床试验取得了可喜的成果。然而,现有策略的局限性包括细胞悬液中输送的 RPE 细胞存活的不确定性以及玻璃体内细胞不受控制增殖的固有风险。人 RPE 干细胞衍生的 RPE(hRPESC-RPE)移植可挽救视网膜营养不良大鼠模型的视力,并在兔视网膜中至少存活 1 个月。本研究将 hRPESC-RPE 单层置于非人类灵长类动物模型的黄斑下 3 个月。移植能够在体内恢复并维持健康的感光细胞。重要的是,没有证据表明亚视网膜移植的单层发生上皮-间充质转化。未观察到邻近视网膜的神经胶质增生或视网膜内膜。这些发现表明 hRPESC-RPE 单层是安全的,可能是 RPE 细胞替代治疗的有用来源。