Restored phagocytic ability of RPE patches derived from gene-corrected retinitis pigmentosa-hiPSCs on a biodegradable scaffold via clinical-grade protocol: implications for autologous therapy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F25%3A00637252" target="_blank" >RIV/61389013:_____/25:00637252 - isvavai.cz</a>

Alternative codes found

RIV/68378041:_____/25:00637252 RIV/67985904:_____/25:00637252

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S2352304225000984?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2352304225000984?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gendis.2025.101609" target="_blank" >10.1016/j.gendis.2025.101609</a>

Result language

angličtina

Original language name

Restored phagocytic ability of RPE patches derived from gene-corrected retinitis pigmentosa-hiPSCs on a biodegradable scaffold via clinical-grade protocol: implications for autologous therapy

Original language description

Cases of hereditary retinal dystrophy (HRD) can be caused by mutations in the MERTK gene, which result in an autosomal recessive form of blindness (Retinitis Pigmentosa - RP) characterized by impaired phagocytosis of photoreceptor outer segments (POS) by retina! pigment epithelial cells (RPE). The continued presence of MERTK gene mutations in patient-derived human induced pluripotent stem cells (hiPSCs) hinders autologous stem cell-based therapies for HRD that aim to replace diseased RPE with in vitro differentiated RPE to prevent photoreceptor dysfunction. We recently reported the generation of an hiPSC model of MERTK-associated RP, which recapitulates HRD phenotypes, and the subsequent creation of gene-corrected RP-hiPSCs using CRISPR/Cas9-mediated gene-editing. The development of RP-hiPSC-RPE under a clinically compatible manufacturing process could bring genetically manipulated cells closer to applications in HRD patients. Here, we applied a clinical-grade differentiation protocol to generate RPE derived from gene-corrected RP-hiPSCs on biodegradable, clinically-approved membrane scaffolds. Functional in vitro validation of such RP­ hiPSC-RPE cells revealed the generation of mature and functional cells, the recovery of wild-type MERTK protein expression, and the phagocytosis of fluorescently-labeled photoreceptor outer segment (POS). Our results set the stage for in vivo preclinical functional and safety evaluation and support the development of future autologous hiPSC-RPE-based therapies for HRDs and other rare vision disorders.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30404 - Biomaterials (as related to medical implants, devices, sensors)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Genes & Diseases

ISSN

2352-4820

e-ISSN

2352-3042

Volume of the periodical

12

Issue of the periodical within the volume

6

Country of publishing house

CN - CHINA

Number of pages

4

Pages from-to

101609

UT code for WoS article

001534944400001

EID of the result in the Scopus database

2-s2.0-105009902941