Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells

Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells

Abstract In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age‐related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function...

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Main Authors: Anna Macečková Brymová, Francisco Javier Rodriguez‐Jimenez, Annika Konrad, Yaroslav Nemesh, Muhammed Arshad Thottappali, Ana Artero‐Castro, Ruslan Nyshchuk, Anastasiia Kolesnikova, Brigitte Müller, Hana Studenovska, Jana Juhasova, Stefan Juhas, Ivona Valekova, Dunja Lukovic, Claudia Aleman, Taras Ardan, Saskia Drutovič, Jan Motlik, Zdenka Ellederova, Zbinek Straňák, Miroslav Veith, Lyubomyr Lytvynchuk, Ruchi Sharma, Kapil Bharti, Goran Petrovski, Pavla Jendelova, Knut Stieger, Slaven Erceg
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
Subjects:
age‐related macular degeneration
cell therapy
Human induced pluripotent stem cells;minipigs
retina
retinal degeneration
retinal pigment epithelium
Online Access:https://doi.org/10.1002/advs.202412301
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Summary:Abstract In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age‐related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function. Repopulating this area with functional RPE cells may prevent or decline the progression of photoreceptor loss. In the present study, the viability, survival, and integration of human induced pluripotent stem cell (hiPSC)‐derived RPE cells (hiPSC‐RPE) is assessed generated using clinical‐grade protocol and cultured on a clinically relevant scaffold (poly‐L‐lactide‐co‐D, L‐lactide, PDLLA) after subretinal implantation in immunosuppressed minipigs for up to 6 weeks. It is shown that transplanted hiPSC‐RPE cells maintain the RPE cell features such as cell polarity, hexagonal shape, and cell–cell contacts, and interact closely with photoreceptor outer segments without signs of gliosis or neuroinflammation throughout the entire period of examination. In addition, an efficient immunosuppressing strategy with a continuous supply of tacrolimus is applied. Continuous verification and improvement of existing protocols are crucial for its translation to the clinic. The results support the use of hiPSC‐RPE on PDLLA scaffold as a cell replacement therapeutic approach for RPE degenerative diseases.
ISSN:2198-3844

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