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. 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.
Authors
- Kapil Bharti (ORCID: https://orcid.org/0000-0003-4884-3173)
- Ana Artero‐Castro (ORCID: https://orcid.org/0000-0003-1362-9994)
- Annika C. Konrad (ORCID: https://orcid.org/0000-0002-7263-9693)
- Ivona Valeková (ORCID: https://orcid.org/0000-0001-5587-0597)
- Slaven Erceg
- Jana Juhásová (ORCID: https://orcid.org/0000-0001-7022-6812)
- Taras Ardan (ORCID: https://orcid.org/0000-0002-4354-8354)
- Zdeňka Ellederová (ORCID: https://orcid.org/0000-0001-6695-6345)
- Muhammed Arshad Thottappali (ORCID: https://orcid.org/0000-0002-3310-8005)
- A. F. Kolesnikova (ORCID: https://orcid.org/0000-0002-7086-7799)
- Anna Brýmová (ORCID: https://orcid.org/0009-0004-8126-1006)
- Hana Studenovská (ORCID: https://orcid.org/0000-0001-7917-1790)
- Lyubomyr Lytvynchuk (ORCID: https://orcid.org/0000-0002-6788-5312)
- Miroslav Veith (ORCID: https://orcid.org/0000-0001-6254-436X)
- Saskia Drutovič (ORCID: https://orcid.org/0000-0002-5103-5073)
- Brigitte Müller (ORCID: https://orcid.org/0000-0001-6514-154X)
- Yaroslav Nemesh (ORCID: https://orcid.org/0000-0003-3862-9413)
- Štefan Juhás (ORCID: https://orcid.org/0000-0002-2866-0727)
- Zbyněk Straňák (ORCID: https://orcid.org/0000-0002-3175-7212)
- Knut Stieger (ORCID: https://orcid.org/0000-0002-8298-5629)
- Pavla Jendelová (ORCID: https://orcid.org/0000-0002-4644-9212)
- Ruslan Nyshchuk (ORCID: https://orcid.org/0000-0002-9838-1547)
- Dunja Lukovic (ORCID: https://orcid.org/0000-0002-4055-4927)
- Goran Petrovski (ORCID: https://orcid.org/0000-0003-2905-9252)
- Ruchi Sharma (ORCID: https://orcid.org/0000-0002-2138-6462)
- Jan Motlík
- Francisco Javier Rodríguez-Jiménez
- Claudia Aleman
Institutions
- Oslo University Hospital (NO)
- University of Oslo (NO)
- Justus-Liebig-Universität Gießen (DE)
- Charles University (CZ)
- University of Szeged (HU)
- Universidad Cardenal Herrera CEU (ES)
- Czech Academy of Sciences, Institute of Animal Physiology and Genetics (CZ)
- Czech Academy of Sciences, Institute of Macromolecular Chemistry (CZ)
- Czech Academy of Sciences, Institute of Experimental Medicine (CZ)
- National Eye Institute (US)
- Centro de Investigacion Principe Felipe (ES)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-04-02
- DOI
- https://doi.org/10.1002/advs.202412301
- Citations
- 5
- Primary Topic
- Retinal Development and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- Fundació la Marató de TV3