Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Stem Cell Reports. 2024 Mar 12;19(3):331-342. doi: 10.1016/j.stemcr.2024.01.005. Epub 2024 Feb 8.
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.
几种视网膜变性会影响人类的中心视网膜，中心视网膜主要由视锥细胞组成，对高分辨率和色觉至关重要。移植视锥细胞是一种很有前途的策略，可以替代该区域已变性的视锥细胞。尽管该方法已在少数几种动物模型中进行了研究，但常用的啮齿动物模型缺乏富含视锥细胞的区域，而较大的模型可能昂贵且难以获得，从而阻碍了治疗方法的转化。在这里，我们将从人诱导多能干细胞分化的视网膜类器官中分离出表达 GFP 的感光细胞移植到受损和未受损的 13 线地松鼠眼的视网膜下腔。通过非侵入性高分辨率成像和免疫组织化学来记录移植细胞的存活情况，以确认在移植后长达 4 个月的时间内存在人供体感光细胞。这些结果表明，使用以视锥细胞为主的啮齿动物模型有助于推进细胞替代疗法的临床转化。
