Human iPSC-derived photoreceptor transplantation in the cone dominant 13-lined ground squirrel

Stem Cell Reports. 2024 Mar 12;19(3):331-342. doi: 10.1016/j.stemcr.2024.01.005. Epub 2024 Feb 8.

Abstract

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.

Keywords: 13-LGS; cone-dominant species; ground squirrels; iPSC; photoreceptor transplantation; retinal organoids; stem cells.

MeSH terms

  • Animals
  • Humans
  • Induced Pluripotent Stem Cells* / transplantation
  • Retina
  • Retinal Cone Photoreceptor Cells / transplantation
  • Retinal Degeneration* / therapy
  • Sciuridae