Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats
- Retinal degenerative disorders, including age-related macular degeneration and retinitis pigmentosa (RP), are characterized by the irreversible loss of photoreceptor cells and retinal pigment epithelial (RPE) cells; however, the long-term effect of implanting both human induced pluripotent stem cell (hiPSC)-derived RPE and photoreceptor for retinal regeneration has not yet been investigated. In this study, we evaluated the long-term effects of hiPSC-derived RPE and photoreceptor cell transplantation in Pde6b knockout rats to study RP; cells were injected into the subretinal space of the right eyes of rats before the appearance of signs of retinal degeneration at 2-3 weeks of age. Ten months after transplantation, we evaluated the cells using fundus photography, optical coherence tomography, and histological evaluation, and no abnormal cell proliferation was observed. A relatively large number of transplanted cells persisted during the first 4 months; subsequently, the number of these cells decreased gradually. Notably, immunohistochemical analysis revealed that the hiPSC-derived retinal cells showed characteristics of both RPE cells and photoreceptors of human origin after transplantation. Functional analysis of vision by scotopic electroretinogram revealed significant preservation of vision after transplantation. Our study suggests that the transplantation of hiPSC-derived retinal cells, including RPE cells and photoreceptors, has a potential therapeutic effect against irreversible retinal degenerative diseases.
Retinal disease: Cell transplants offer hope Cells with the potential to regenerate retinal cells could become a useful treatment for serious eye diseases such as age-related macular degeneration and retinitis pigmentosa. The retina has only limited self-regenerating potential. Joo Yong Lee and colleagues at the University of Ulsan in Seoul, South Korea, studied the long-term effects of implanting cells derived from human stem cells into the eyes of rats that had been genetically modified to act as a model of retinal degenerative disease. The implanted cells have the features of the photoreceptor cells that detect light and those cells that generate a layer of the retina called the retinal pigment epithelium. A substantial population of the cells persisted for at least four months, significantly preserving the animals' vision. The results justify further exploration of the therapeutic possibilities.
- 강은주; 김보라; 소성준; 양지명; 윤경아; 이주용; 정선호
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- Age; Allografts; Cell proliferation; Epithelium; Eye diseases; Long-term effects; Macular degeneration; Phosphodiesterase; Photography; Photoreceptors; Pluripotency; Retina; Retinal degeneration; Retinal pigment epithelium; Retinitis; Retinitis pigmentosa; Stem cell transplantation; Stem cells; Stem-cell research; Translational research; Transplants & implants; Vision; 생화학
- EXPERIMENTAL AND MOLECULAR MEDICINE
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