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Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats

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Abstract
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.
Author(s)
강은주김보라소성준양지명윤경아이주용정선호
Issued Date
2021
Type
Article
Keyword
AgeAllograftsCell proliferationEpitheliumEye diseasesLong-term effectsMacular degenerationPhosphodiesterasePhotographyPhotoreceptorsPluripotencyRetinaRetinal degenerationRetinal pigment epitheliumRetinitisRetinitis pigmentosaStem cell transplantationStem cellsStem-cell researchTranslational researchTransplants & implantsVision생화학
DOI
10.1038/s12276-021-00588-w
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7653
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_nrf_kci_oai_kci_go_kr_ARTI_9774280&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Long-term%20effects%20of%20human%20induced%20pluripotent%20stem%20cell-derived%20retinal%20cell%20transplantation%20in%20Pde6b%20knockout%20rats&offset=0&pcAvailability=true
Publisher
EXPERIMENTAL AND MOLECULAR MEDICINE
Location
대한민국
Language
영어
ISSN
1226-3613
Citation Volume
53
Citation Number
4
Citation Start Page
631
Citation End Page
642
Appears in Collections:
Medicine > Medicine
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