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

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. Repopul...

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Detalles Bibliográficos
Autores: Brymová, AM, Rodriguez-Jimenez, FJ, Konrad, A, Nemesh, Y, Thottappali, MA, Artero-Castro, A, Nyshchuk, R, Kolesnikova, A, Müller, B, Studenovska, H, Juhasova, J, Juhas, S, Valekova, I, Lukovic, D, Aleman, C, Ardan, T, Drutovic, S, Motlik, J, Ellederova, Z, Stranák, Z, Veith, M, Lytvynchuk, L, Sharma, R, Bharti, K, Petrovski, G, Jendelova, P, Stieger, K, Erceg, S
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Centro de Investigación Principe Felipe (CIPF)
Repositorio:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p4560
Acceso en línea:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4560
Access Level:acceso abierto
Palabra clave:age-related macular degeneration
cell therapy
Human induced pluripotent stem cells
minipigs
retina
retinal degeneration
retinal pigment epithelium
Descripción
Sumario: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.

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