Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes

IF 20.4 1区医学 Q1 CELL & TISSUE ENGINEERING

Cell stem cell Pub Date : 2025-09-16 DOI:10.1016/j.stem.2025.08.012

Rajesh C. Rao, Brigitte L. Arduini, Susan Borden, Dhruv Sareen, Clive Svendsen, Paul Lee, Charles Ryan, Shilpa Kodati, Caroline Nyaiburi, Keith Wolsieffer, Eric Oh, Shuna Park, Glenna Ford, Keith Dionne, Sally Temple, Jeffrey Stern

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Abstract

Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD.

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干性年龄相关性黄斑变性患者RPESC-RPE移植的安全性和耐受性：低剂量临床结果

干性年龄相关性黄斑变性（AMD）视网膜色素上皮（RPE）细胞萎缩损害感光细胞功能，导致视力丧失。基于干细胞的RPE替代疗法旨在逆转疾病进展并恢复视力。RPESC-RPE- 4w是一种有丝分裂后成人RPE干细胞衍生的RPE （RPESC-RPE）祖细胞产品，在临床前研究中显示出一致的安全性和有效性。RPESC-RPE-4W的首次人体临床试验完成了低剂量队列1干预（NCT04627428）。6名受试者接受了50,000个RPESC-RPE-4W细胞的视网膜下悬浮。未观察到明显的炎症、肿瘤或与产品相关的严重不良事件。三名视力较差的A组受试者的最佳矫正视力在12个月时比基线平均提高了21.67个字母。三个视力较好的B组受试者在6个月时平均提高了+3.0个字母。低剂量队列1的阳性安全性和耐受性结果使剂量增加到中剂量RPESC-RPE-4W治疗干性AMD。

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来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.