Back to Search
Start Over
Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2011 Aug; Vol. 29 (8), pp. 1206-18. - Publication Year :
- 2011
-
Abstract
- 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.<br /> (Copyright © 2011 AlphaMed Press.)
- Subjects :
- Carrier Proteins genetics
Carrier Proteins metabolism
Cell Line
Gene Expression
Genetic Therapy
Gyrate Atrophy pathology
Humans
Intercellular Signaling Peptides and Proteins genetics
Intercellular Signaling Peptides and Proteins metabolism
Membrane Potentials
Patch-Clamp Techniques
Photoreceptor Cells metabolism
Photoreceptor Cells pathology
Photoreceptor Cells physiology
Precision Medicine
Prosencephalon embryology
Retina embryology
Retina pathology
Retinal Pigment Epithelium pathology
Transcription Factors genetics
Transcription Factors metabolism
Drug Evaluation, Preclinical methods
Pluripotent Stem Cells physiology
Retinal Diseases therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1549-4918
- Volume :
- 29
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 21678528
- Full Text :
- https://doi.org/10.1002/stem.674