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视网膜类器官在视网膜疾病治疗中的应用前景。

The Prospects for Retinal Organoids in Treatment of Retinal Diseases.

机构信息

Biomedical Engineering, University of California, Irvine, CA.

Stem Cell Research Center, University of California, Irvine, CA.

出版信息

Asia Pac J Ophthalmol (Phila). 2022;11(4):314-327. doi: 10.1097/APO.0000000000000538. Epub 2022 Aug 30.

Abstract

Retinal degeneration (RD) is a significant cause of incurable blindness worldwide. Photoreceptors and retinal pigmented epithelium are irreversibly damaged in advanced RD. Functional replacement of photoreceptors and/or retinal pigmented epithelium cells is a promising approach to restoring vision. This paper reviews the current status and explores future prospects of the transplantation therapy provided by pluripotent stem cell-derived retinal organoids (ROs). This review summarizes the status of rodent RD disease models and discusses RO culture and analytical tools to evaluate RO quality and function. Finally, we review and discuss the studies in which RO-derived cells or sheets were transplanted. In conclusion, methods to derive ROs from pluripotent stem cells have significantly improved and become more efficient in recent years. Meanwhile, more novel technologies are applied to characterize and validate RO quality. However, opportunity remains to optimize tissue differentiation protocols and achieve better RO reproducibility. In order to screen high-quality ROs for downstream applications, approaches such as noninvasive and label-free imaging and electrophysiological functional testing are promising and worth further investigation. Lastly, transplanted RO-derived tissues have allowed improvements in visual function in several RD models, showing promises for clinical applications in the future.

摘要

视网膜变性(RD)是全球范围内导致不可治愈失明的主要原因。在晚期 RD 中,感光细胞和视网膜色素上皮细胞不可逆转地受损。功能性替代感光细胞和/或视网膜色素上皮细胞是恢复视力的一种很有前途的方法。本文综述了多能干细胞衍生的视网膜类器官(RO)移植治疗的现状,并探讨了其未来前景。本文总结了啮齿动物 RD 疾病模型的现状,并讨论了 RO 培养和分析工具,以评估 RO 的质量和功能。最后,我们综述和讨论了 RO 衍生细胞或薄片移植的研究。总之,近年来,从多能干细胞中衍生 RO 的方法得到了显著改善,效率也有所提高。同时,更多的新技术被应用于 RO 质量的表征和验证。然而,仍有机会优化组织分化方案,提高 RO 的可重复性。为了筛选出用于下游应用的高质量 RO,非侵入性和无标记成像和电生理功能测试等方法具有很大的发展潜力,值得进一步研究。最后,移植的 RO 衍生组织已经在几种 RD 模型中改善了视觉功能,为未来的临床应用带来了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2dd/9966053/144383b01e86/nihms-1874714-f0001.jpg

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