Extensive monolayer formation after transplantation depends on an RPE subpopulation derived from human iPSCs

IF 4.5 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2026-11-20 Epub Date: 2026-10-07 DOI:10.1016/j.isci.2026.117750

Karen Tessmer, Juliane Hammer, Sylvia J. Gasparini, Klara Schmidtke, Trishla Adhikari, Lea Michalke, Anne Schön, Flavia Sulaj, Liliana R. Loureiro, Annika Last, Nadine Chelius, Annett Kurtz, Hannah Johannsen, Madalena Carido, Susanne Ferguson, Andreas Petzold, Ulrike A. Friedrich, Thomas Kurth, Andreas Dahl, Anja Feldmann, Marius Ader

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Abstract

•
Polarized monolayer formation by hiPSC-derived RPE suspensions in RPE-depleted mice
•
Transplant-derived RPE monolayers phagocytose host outer segments
•
Monolayer proportion is increased in passage 1 vs. passage 2 RPE cells
•
Isolation of a monolayer-forming RPE subpopulation by CD54⁺/PSA-NCAM⁻ sorting

Loss of retinal pigment epithelium (RPE) in the eye leads to photoreceptor dysfunction, death, and eventually, vision loss. Cell replacement strategies using RPE cells derived in vitro from pluripotent stem cells are currently evaluated as a potential therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function; however, monolayer formation following transplantation of RPE suspensions has not been systematically assessed. Using the sodium iodate mouse model of acute RPE depletion, significant increase in monolayer formation capacity of passage 1 vs. 2 human induced pluripotent stem cell (iPSC)-derived RPE cells was observed three weeks post-transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM⁻ was identified to enrich for an RPE subpopulation with a high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.

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移植后广泛的单层形成依赖于来自人类iPSCs的RPE亚群

•移植来源的RPE单层吞噬宿主外节段•第1代RPE细胞中单层比例比第2代RPE细胞中单层比例增加•通过CD54+/PSA-NCAM -分选分离形成单层的RPE亚群眼睛视网膜色素上皮（RPE）的缺失导致光受体功能障碍、死亡，并最终导致视力丧失。利用多能干细胞衍生的体外RPE细胞进行细胞替代策略目前被评估为一种潜在的治疗策略。极化单层膜的产生是正确的RPE功能的必要先决条件；然而，RPE悬浮液移植后的单层形成尚未系统评估。利用碘酸钠小鼠急性RPE耗竭模型，观察到1代人诱导多能干细胞（iPSC）衍生的RPE细胞在移植后3周的单层形成能力显著增加。移植来源的单层细胞具有特征性的顶基极性、RPE标记表达、吞噬功能和宿主外核层的保存。细胞表面标记板CD54+/PSA-NCAM -被鉴定为RPE亚群富集，在移植后具有高的单层形成潜力。结果强调了定义和分离能态细胞亚群对于成功的RPE移植的重要性。眼内视网膜色素上皮（RPE）的丧失可导致光感受器功能障碍、死亡，并最终导致视力丧失。利用多能干细胞衍生的体外RPE细胞进行细胞替代策略目前被评估为一种潜在的治疗策略。极化单层膜的产生是正确的RPE功能的必要先决条件；然而，RPE悬浮液移植后的单层形成尚未系统评估。利用碘酸钠小鼠急性RPE耗竭模型，观察到1代人诱导多能干细胞（iPSC）衍生的RPE细胞在移植后3周的单层形成能力显著增加。移植来源的单层细胞具有特征性的顶基极性、RPE标记表达、吞噬功能和宿主外核层的保存。细胞表面标记板CD54+/PSA-NCAM -被鉴定为RPE亚群富集，在移植后具有高的单层形成潜力。结果强调了定义和分离能态细胞亚群对于成功的RPE移植的重要性。下载：下载高清图片（219KB）下载：下载全尺寸图片

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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