Journal
STEM CELLS
Volume 29, Issue 8, Pages 1206-1218Publisher
WILEY
DOI: 10.1002/stem.674
Keywords
Pluripotent stem cells; Retina; Developmental Biology; Neural differentiation; Cellular therapy; Induced pluripotent stem cell
Categories
Funding
- Foundation Fighting Blindness
- NIH [R01EY21218, P30HD03352]
- Lincy Foundation
- Retina Research Foundation (RRF)
- E. Matilda Ziegler Foundation
- UW-ICTR NIH [1UL1RR025011]
- Research to Prevent Blindness
- UW Eye Research Institute/RRF Murfee Chair
- NHMRC
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Differentiation methods for human induced pluripotent stem cells (hiPSCs) typically yield progeny from multiple tissue lineages, limiting their use for drug testing and autologous cell transplantation. In particular, early retina and forebrain derivatives often intermingle in pluripotent stem cell cultures, owing to their shared ancestry and tightly coupled development. Here, we demonstrate that three-dimensional populations of retinal progenitor cells (RPCs) can be isolated from early forebrain populations in both human embryonic stem cell and hiPSC cultures, providing a valuable tool for developmental, functional, and translational studies. Using our established protocol, we identified a transient population of optic vesicle (OV)like structures that arose during a time period appropriate for normal human retinogenesis. These structures were independently cultured and analyzed to confirm their multipotent RPC status and capacity to produce physiologically responsive retinal cell types, including photoreceptors and retinal pigment epithelium (RPE). We then applied this method to hiPSCs derived from a patient with gyrate atrophy, a retinal degenerative disease affecting the RPE. RPE generated from these hiPSCs exhibited a disease-specific functional defect that could be corrected either by pharmacological means or following targeted gene repair. The production of OV-like populations from human pluripotent stem cells should facilitate the study of human retinal development and disease and advance the use of hiPSCs in personalized medicine. STEM CELLS 2011; 29: 1206-1218
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