Sakai Daiki, Mandai Michiko, Hirami Yasuhiko, Yamamoto Midori, Ito Shin-Ichiro, Igarashi Saori, Yokota Satoshi, Uyama Hirofumi, Fujihara Masashi, Maeda Akiko, Terada Motoki, Nishida Mitsuhiro, Shibata Yumiko, Hayashi Naoko, Iseki Kyoko, Miura Takuya, Kajita Keisuke, Ishida Masaaki, Sugita Sunao, Maeda Tadao, Takahashi Masayo, Kurimoto Yasuo
Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan.
Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan.
Ophthalmol Sci. 2025 Mar 18;5(4):100770. doi: 10.1016/j.xops.2025.100770. eCollection 2025 Jul-Aug.
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.
Single-arm, open-label, interventional study.
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 -associated retinitis pigmentosa.
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.
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.
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.
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.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
探讨异体诱导多能干细胞（iPSC）来源的视网膜色素上皮（RPE）条带移植治疗RPE变性患者的安全性和有效性。
单臂、开放标签干预性研究。
3例临床诊断为RPE损伤疾病患者的3只眼；1例患有干性年龄相关性黄斑变性（AMD），其余2例患有相关色素性视网膜炎。
通过25G经睫状体平坦部玻璃体切除术进行异体iPSC来源的RPE条带移植。RPE条带通过将iPSC来源的RPE细胞在模具中2毫米宽的凹槽中孵育制备。使用38G视网膜下套管制造人工视网膜脱离，并使用31G套管将RPE条带注入视网膜下液泡，最大移植剂量限制为2条。
通过移植异体iPSC来源的RPE细胞植入减少RPE异常区域，通过在移植前和移植后长达52周使用自动评估程序分析荧光素血管造影来测量。
在移植后52周时，所有患者均达到了通过移植的移植物细胞存活来减少RPE异常区域的主要终点。视觉功能评估证实，1例干性AMD患者的视力相关生活质量有显著改善，视网膜敏感性有潜在恢复。在手术期间和手术后立即证实了iPSC来源的RPE条带成功进行视网膜下递送。在所有患者中，使用偏振敏感光学相干断层扫描（OCT）特异性观察到从条带迁移出的RPE细胞植入，并通过自适应光学成像将其可视化为特征性六边形细胞。虽然未发生严重不良事件，但分别在1例患者中观察到对移植物细胞的疑似免疫反应和视网膜前膜形成。
在所有3例患者中，通过可靠递送异体iPSC来源的RPE条带实现了RPE异常区域的减少，且未发生严重不良事件。需要进一步进行长期研究和纳入术前视力更好的更大队列，以评估RPE条带移植的安全性和有效性。
专有或商业披露信息可在本文末尾的脚注和披露中找到。
