Mandai Michiko
Research Center, Kobe City Eye Hospital, Minatojima Minamimachi 2-1-8, Chuo-ku, Kobe Hyogo, 650-0047, Japan.
Regen Ther. 2023 Jan 5;22:59-67. doi: 10.1016/j.reth.2022.12.005. eCollection 2023 Mar.
In recent decades, many researchers have attempted to restore vision via transplantation of retina/retinal cells in eyes with retinal degeneration. The advent of induced pluripotent stem cells (iPSC) and retinal organoid induction technologies has boosted research on retinal regeneration therapy. Although the recognition of functional integration of graft photoreceptor cells in the host retina from 2006 has been disputed a decade later by the newly evidenced phenomenon denoted as "material transfer," several reports support possible reconstruction of the host-graft network in the retinas of both end-stage degeneration and in progressing degeneration cases. Based on proof of concept (POC) studies in animal models, a clinical study was conducted in Kobe, Japan in 2020 and showed the feasibility of cell-based therapy using iPSC retinal organoid technology. Although the graft potency of human embryonic stem (ES)/iPS cell-derived retinal organoid/retinal cells has been suggested by previous studies, much is still unknown regarding host capability, that is, how long-standing human degenerating retinas are capable of rewiring with transplanted cells. This review summarizes past POC studies on photoreceptor replacement therapy and introduces some new challenges to maximize the possible efficacy in future human clinical studies of regenerative therapy.
近几十年来，许多研究人员试图通过向患有视网膜变性的眼睛移植视网膜/视网膜细胞来恢复视力。诱导多能干细胞（iPSC）和视网膜类器官诱导技术的出现推动了视网膜再生治疗的研究。尽管从2006年开始人们认识到移植的光感受器细胞在宿主视网膜中的功能整合，但十年后，一种新发现的被称为“物质转移”的现象对此提出了质疑，不过仍有几份报告支持在晚期变性和进行性变性病例的视网膜中可能重建宿主-移植物网络。基于动物模型的概念验证（POC）研究，2020年在日本神户进行了一项临床研究，结果显示了使用iPSC视网膜类器官技术进行细胞治疗的可行性。尽管先前的研究表明了人胚胎干细胞（ES）/iPS细胞来源的视网膜类器官/视网膜细胞的移植潜力，但关于宿主能力，即长期存在的人类变性视网膜与移植细胞重新建立连接的能力，仍有许多未知之处。这篇综述总结了过去关于光感受器替代疗法的POC研究，并介绍了一些新的挑战，以便在未来人类再生治疗临床研究中最大限度地提高可能的疗效。
