1. Directed Differentiation of Human Embryonic Stem Cells into Functional Retinal Pigment Epithelium Cells
- Author
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Sharona Even-Ram, Yoav Smith, Benjamin Reubinoff, Nurit Yachimovich-Cohen, Yael Berman-Zaken, Alexey Obolensky, Ruslana Alper, Etti Ben-Shushan, Hanita Khaner, Ofer Wiser, Michal Gropp, Gideon Rechavi, Itzhak Hemo, Eyal Banin, Maria Idelson, Malkiel A. Cohen, and Limor Matzrafi
- Subjects
Retinal degeneration ,Cell Transplantation ,Activin Receptors, Type II ,Retinal Pigment Epithelium ,Biology ,Polymerase Chain Reaction ,Cell Line ,Immunophenotyping ,Directed differentiation ,Microscopy, Electron, Transmission ,Transforming Growth Factor beta ,Retinitis pigmentosa ,medicine ,Genetics ,Animals ,Humans ,Microscopy, Phase-Contrast ,Embryonic Stem Cells ,Retina ,Retinal pigment epithelium ,Cell Differentiation ,Epithelial Cells ,Anatomy ,Cell Biology ,medicine.disease ,Flow Cytometry ,Embryonic stem cell ,STEMCELL ,eye diseases ,Cell biology ,Activins ,Rats ,Transplantation ,medicine.anatomical_structure ,embryonic structures ,Molecular Medicine ,Fibroblast Growth Factor 2 ,sense organs ,Stem cell ,Activin Receptors, Type I - Abstract
SummaryDysfunction and loss of retinal pigment epithelium (RPE) leads to degeneration of photoreceptors in age-related macular degeneration and subtypes of retinitis pigmentosa. Human embryonic stem cells (hESCs) may serve as an unlimited source of RPE cells for transplantation in these blinding conditions. Here we show the directed differentiation of hESCs toward an RPE fate under defined culture conditions. We demonstrate that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate. In the presence of nicotinamide, factors from the TGF-β superfamily, which presumably pattern RPE development during embryogenesis, further direct RPE differentiation. The hESC-derived pigmented cells exhibit the morphology, marker expression, and function of authentic RPE and rescue retinal structure and function after transplantation to an animal model of retinal degeneration caused by RPE dysfunction. These results are an important step toward the future use of hESCs to replenish RPE in blinding diseases.
- Published
- 2009
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