Human iPSC-derived photoreceptor transplantation in the cone dominant 13-lined ground squirrel
Several retinal degenerations affect the human central retina, which is primarily comprised of cones and is essential for high acuity and color vision. Transplanting cone photoreceptors is a promising strategy to replace degenerated cones in this region. Although this approach has been investigated...
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Veröffentlicht in: | Stem cell reports 2024-03, Vol.19 (3), p.331-342 |
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Sprache: | eng |
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Zusammenfassung: | Several retinal degenerations affect the human central retina, which is primarily comprised of cones and is essential for high acuity and color vision. Transplanting cone photoreceptors is a promising strategy to replace degenerated cones in this region. Although this approach has been investigated in a handful of animal models, commonly used rodent models lack a cone-rich region and larger models can be expensive and inaccessible, impeding the translation of therapies. Here, we transplanted dissociated GFP-expressing photoreceptors from retinal organoids differentiated from human induced pluripotent stem cells into the subretinal space of damaged and undamaged cone-dominant 13-lined ground squirrel eyes. Transplanted cell survival was documented via noninvasive high-resolution imaging and immunohistochemistry to confirm the presence of human donor photoreceptors for up to 4 months posttransplantation. These results demonstrate the utility of a cone-dominant rodent model for advancing the clinical translation of cell replacement therapies.
•Successful integration of hiPSC photoreceptors was observed in the 13-LGS retina•Noninvasive longitudinal imaging traced transplanted cells for up to 4 months•Maturation structures resembling inner segments was visualized using AOSLO imaging•Degree of integration was related to type of damage in the induced 13-LGS models
Yu and colleagues showed that human iPSC-derived photoreceptors generated from 3D-retinal organoids could survive up to 4 months following transplantation in the cone-dominant 13-lined ground squirrel retina. The degree of integration and intraretinal localization of the transplanted cells appeared to depend on the degree of retinal damage. |
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ISSN: | 2213-6711 2213-6711 |
DOI: | 10.1016/j.stemcr.2024.01.005 |