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

人类 iPSC 衍生的光感受器移植到视锥细胞占主导地位的 13 线地松鼠中

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作者:Ching Tzu Yu, Sangeetha Kandoi, Ramesh Periasamy, L Vinod K Reddy, Hannah M Follett, Phyllis Summerfelt, Cassandra Martinez, Chloe Guillaume, Owen Bowie, Thomas B Connor, Daniel M Lipinski, Kenneth P Allen, Dana K Merriman, Joseph Carroll, Deepak A Lamba

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.

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