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
Hauptverfasser: Yu, Ching Tzu, Kandoi, Sangeetha, Periasamy, Ramesh, Reddy, L. Vinod K., Follett, Hannah M., Summerfelt, Phyllis, Martinez, Cassandra, Guillaume, Chloe, Bowie, Owen, Connor, Thomas B., Lipinski, Daniel M., Allen, Kenneth P., Merriman, Dana K., Carroll, Joseph, Lamba, Deepak A.
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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.
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2024.01.005