Generation of Retinal Pigment Epithelial Cells from Small Molecules and OCT4 Reprogrammed Human Induced Pluripotent Stem Cells
Overview
Pharmacology
Authors
Affiliations
Autologous retinal pigment epithelium (RPE) grafts derived from induced pluripotent stem cells (iPSCs) may be used to cure blinding diseases in which RPE dysfunction results in photoreceptor degeneration. Four-, two-, and one-factor-derived iPSCs (4F-, 2F-, and 1F-iPSCs, respectively) were differentiated into fully functional cuboidal pigmented cells in polarized monolayers that express RPE-specific markers. 1F-iPSCs-RPE (1F-iPS-RPE) strongly resembles primary human fetal RPE (hfRPE) based on proteomic and untargeted metabolomic analyses, and using novel in vivo imaging technology coupled with electroretinography, we demonstrated that 1F-iPS-RPE mediate anatomical and functional rescue of photoreceptors after transplantation in an animal model of RPE-mediated retinal degeneration. 1F-iPS0RPE cells were injected subretinally as a suspension and formed a monolayer dispersed between host RPE cells. Furthermore, 1F-iPS-RPE do not simply provide trophic support to rescue photoreceptors as previously speculated but actually phagocytose photoreceptor outer segments in vivo and maintain visual cycling. Thus, 1f-iPS-RPE grafts may be superior to conventional iPS-RPE for clinical use because 1F-IPS-RPE closely resemble hfRPE, mediate anatomical and functional photoreceptor rescue in vivo, and are generated using a reduced number of potentially oncogenic reprogramming factors.
Generation of Induced-Primary Retinal Pigment Epithelium from Human Retinal Organoids.
Flores-Bellver M, Canto-Soler M Methods Mol Biol. 2024; 2848:197-214.
PMID: 39240525 DOI: 10.1007/978-1-0716-4087-6_13.
Retina regeneration: lessons from vertebrates.
Sharma P, Ramachandran R Oxf Open Neurosci. 2024; 1:kvac012.
PMID: 38596712 PMC: 10913848. DOI: 10.1093/oons/kvac012.
Collin J, Hasoon M, Zerti D, Hammadi S, Dorgau B, Clarke L Hum Mol Genet. 2023; 32(10):1698-1710.
PMID: 36645183 PMC: 10162434. DOI: 10.1093/hmg/ddad007.
Oxidative stress and mitochondrial transfer: A new dimension towards ocular diseases.
Subramaniam M, Iyer M, Nair A, Venkatesan D, Mathavan S, Eruppakotte N Genes Dis. 2022; 9(3):610-637.
PMID: 35782976 PMC: 9243399. DOI: 10.1016/j.gendis.2020.11.020.
A stem cell journey in ophthalmology: From the bench to the clinic.
Caras I, Collins L, Creasey A Stem Cells Transl Med. 2021; 10(12):1581-1587.
PMID: 34515419 PMC: 8641078. DOI: 10.1002/sctm.21-0239.