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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

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

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Genes & Diseases

ISSN

2352-4820

e-ISSN

2352-3042

Svazek periodika

12

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

CN - Čínská lidová republika

Počet stran výsledku

4

Strana od-do

101609

Kód UT WoS článku

001534944400001

EID výsledku v databázi Scopus

2-s2.0-105009902941