Open AccessGeneration of Retinal Pigment Epithelial Cells from Small Molecules and OCT4 Reprogrammed Human Induced Pluripotent Stem Cells
Author(s) -
Krohne Tim U.,
Westenskow Peter D.,
Kurihara Toshihide,
Friedlander David F.,
Lehmann Mandy,
Dorsey Alison L.,
Li Wenlin,
Zhu Saiyong,
Schultz Andrew,
Wang Junhua,
Siuzdak Gary,
Ding Sheng,
Friedlander Martin
Publication year - 2012
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.5966/sctm.2011-0057
Subject(s) - induced pluripotent stem cell , retinal pigment epithelium , microbiology and biotechnology , biology , reprogramming , retinal , retinal degeneration , transplantation , retina , retinal regeneration , stem cell , embryonic stem cell , neuroscience , regeneration (biology) , cell , medicine , genetics , biochemistry , surgery , gene
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‐iPSC‐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‐iPS‐RPE 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.