Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-03-18 DOI:10.1016/j.xops.2025.100770

Daiki Sakai MD , Michiko Mandai MD, PhD , Yasuhiko Hirami MD, PhD , Midori Yamamoto BA , Shin-ichiro Ito MD, PhD , Saori Igarashi MD , Satoshi Yokota MD, PhD , Hirofumi Uyama MD, PhD , Masashi Fujihara MD, PhD , Akiko Maeda MD, PhD , Motoki Terada BS , Mitsuhiro Nishida MS , Yumiko Shibata MS , Naoko Hayashi MS , Kyoko Iseki MA , Takuya Miura MS , Keisuke Kajita MD, PhD , Masaaki Ishida MD, PhD , Sunao Sugita MD, PhD , Tadao Maeda MD, PhD , Yasuo Kurimoto MD, PhD

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Abstract

Purpose

To explore the safety and efficacy of the allogeneic induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) strip transplantation for patients with RPE degeneration.

Design

Single-arm, open-label, interventional study.

Participants

Three eyes from 3 patients clinically diagnosed with RPE impairment disease; 1 patient had dry age-related macular degeneration (AMD), and remaining 2 patients had MERTK-associated retinitis pigmentosa.

Intervention

Allogeneic iPSC-derived RPE strip transplantation was performed by a 25-gauge pars plana vitrectomy. The RPE strips were prepared by incubating iPSC-derived RPE cells in 2-mm-wide grooves in the mold. Artificial retinal detachment was generated using a 38-gauge subretinal cannula, and the RPE strips were injected into the retinal bleb using a 31-gauge cannula with the maximum graft dose limited to 2 strips.

Main Outcome Measures

The reduction of RPE abnormal area by the engraftment of transplanted allogeneic iPSC-derived RPE cells, which was measured by analyzing fluorescein angiography with an automated evaluation program at pretransplantation and up to 52 weeks posttransplantation.

Results

The primary endpoint of reducing abnormal areas of RPE through the survival of the transplanted graft cells was achieved in all patients at 52 weeks posttransplantation. Visual function assessments confirmed significant vision-related quality of life improvement and potential retinal sensitivity restoration in 1 patient with dry AMD. The successful subretinal delivery of the iPSC-derived RPE strips was confirmed during and immediately after surgery. The engraftment of RPE cells migrated out from the strips was observed using polarization-sensitive OCT specifically and visualized as characteristic hexagonal cells via adaptive optics imaging in all patients. While no serious adverse events occurred, suspected immune reactions to graft cells and epiretinal membrane formation were observed in 1 patient each.

Conclusions

A decrease in the RPE abnormal area by reliable delivery of allogeneic iPSC-derived RPE strips was achieved in all 3 cases with no serious adverse events. Further long-term studies and larger cohorts with better preoperative vision are warranted to evaluate the safety and efficacy of RPE strip transplantation.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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诱导多能干细胞来源视网膜色素上皮条移植治疗黄斑变性和视网膜色素变性

目的探讨同种异体诱导多能干细胞（iPSC）源性视网膜色素上皮（RPE）条带移植治疗视网膜色素上皮变性的安全性和有效性。设计：单臂、开放标签、介入研究。临床诊断为RPE损伤性疾病的3例患者的3只眼；1例为干性老年性黄斑变性（AMD），其余2例为mertk相关色素性视网膜炎。介入异基因ipsc衍生的RPE条带移植通过25号玻璃体切割完成。将ipsc衍生的RPE细胞培养在模具中2 mm宽的凹槽中制备RPE条带。采用38号视网膜下套管制造人工视网膜脱离，并采用31号套管将RPE条注入视网膜泡内，最大移植剂量限制为2条。通过移植同种异体ipsc衍生的RPE细胞，通过荧光素血管造影分析，在移植前和移植后52周内自动评估RPE异常区域的减少。结果所有患者在移植后52周均达到了通过移植细胞存活减少RPE异常区域的主要终点。视觉功能评估证实了1例干性AMD患者显著的视觉相关生活质量改善和潜在的视网膜敏感性恢复。在手术期间和手术后立即证实了ipsc衍生的RPE条在视网膜下的成功递送。在所有患者中，通过偏振敏感OCT特异性观察到RPE细胞从条带中迁移出来，并通过自适应光学成像显示为特征性六边形细胞。在未发生严重不良事件的情况下，各有1例患者观察到疑似移植细胞免疫反应和视网膜前膜形成。结论3例患者均通过可靠的异体ipsc来源的RPE条带减少了RPE异常区域，无严重不良事件发生。需要进一步的长期研究和术前视力较好的更大的队列来评估RPE条带移植的安全性和有效性。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

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