继承性视网膜退行性病变是发达国家中不可治愈的视力损失的主要原因。虽然自体诱导多能干细胞介导的光感受器细胞替代在理论上是可能的，但缺乏专门设计用于启用特定患者治疗的高通量并行生产的商业可用技术，已妨碍了临床研究。在这项研究中，我们描述了使用Cell X精密机器人细胞培养平台以启用临床级别患者特异性iPSCs的并行生产。Cell X位于符合ISO 5级cGMP标准的封闭无菌隔离器（Biospherix XVivo X2）内，从成纤维细胞培养到iPSC生成、克隆扩增和视网膜分化的所有程序均在其中执行。运用评分卡分析确定使用Cell X平台生成的患者iPSCs是多能的，并通过核型分析确保其具有遗传稳定性。通过免疫染色和共聚焦显微镜确定，使用Cell X平台生成的iPSCs产生的视网膜器官样体与手动生成的iPSCs产生的样本无异。此外，在分化后120天的单细胞RNA测序分析中，使用Cell X平台生成的细胞与在另一个实验室中手动条件生成的细胞相当。我们已成功开发了机器人iPSC生成平台和标准操作程序，用于生产与当前良好制造实践相容的高质量光感受器前体细胞。此系统将启用自体视网膜细胞替代的临床级别iPSC生产。 ©2023 作者。

Inherited retinal degeneration is a leading cause of incurable vision loss in the developed world. While autologous iPSC mediated photoreceptor cell replacement is theoretically possible, the lack of commercially available technologies designed to enable high throughput parallel production of patient specific therapeutics has hindered clinical translation.In this study, we describe the use of the Cell X precision robotic cell culture platform to enable parallel production of clinical grade patient specific iPSCs. The Cell X is housed within an ISO Class 5 cGMP compliant closed aseptic isolator (Biospherix XVivo X2), where all procedures from fibroblast culture to iPSC generation, clonal expansion and retinal differentiation were performed.Patient iPSCs generated using the Cell X platform were determined to be pluripotent via score card analysis and genetically stable via karyotyping. As determined via immunostaining and confocal microscopy, iPSCs generated using the Cell X platform gave rise to retinal organoids that were indistinguishable from organoids derived from manually generated iPSCs. In addition, at 120 days post-differentiation, single-cell RNA sequencing analysis revealed that cells generated using the Cell X platform were comparable to those generated under manual conditions in a separate laboratory.We have successfully developed a robotic iPSC generation platform and standard operating procedures for production of high-quality photoreceptor precursor cells that are compatible with current good manufacturing practices. This system will enable clinical grade production of iPSCs for autologous retinal cell replacement.© 2023. The Author(s).