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Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells
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Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells
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Journal Article
Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells
2025
Overview
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. Human induced pluripotent stem cell‐derived retinal pigment epithelial (hiPSC‐RPE) cells, cultured on a clinically relevant PDLLA scaffold, are transplanted into immunosuppressed minipigs. The study demonstrates the viability, integration, and preservation of RPE‐specific features without gliosis or neuroinflammation, supporting their potential as a cell replacement therapy for retinal degenerative diseases.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
age‐related macular degeneration
/ Animals
/ Human induced pluripotent stem cells;minipigs
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - transplantation
/ Macular Degeneration - therapy
/ Retina
/ Retinal Pigment Epithelium - cytology
/ Retinal Pigment Epithelium - transplantation
/ Swine
