title: Brief report: self-organizing neuroepithelium from human pluripotent stem cells facilitates derivation of photoreceptors.
abstract: Retinitis pigmentosa, other inherited retinal diseases, and age-related macular degeneration lead to untreatable blindness because of the loss of photoreceptors. We have recently shown that transplantation of mouse photoreceptors can result in improved vision. It is therefore timely to develop protocols for efficient derivation of photoreceptors from human pluripotent stem (hPS) cells. Current methods for photoreceptor derivation from hPS cells require long periods of culture and are rather inefficient. Here, we report that formation of a transient self-organized neuroepithelium from human embryonic stem cells cultured together with extracellular matrix is sufficient to induce a rapid conversion into retinal progenitors in 5 days. These retinal progenitors have the ability to differentiate very efficiently into Crx(+) photoreceptor precursors after only 10 days and subsequently acquire rod photoreceptor identity within 4 weeks. Directed differentiation into photoreceptors using this protocol is also possible with human-induced pluripotent stem (hiPS) cells, facilitating the use of patient-specific hiPS cell lines for regenerative medicine and disease modeling.
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Cédric
authors.initials: C
authors.lastname: Boucherie
authors.forename: Sayandip
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Els
authors.initials: E
authors.lastname: Henckaerts
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: Jane C
authors.initials: JC
authors.lastname: Sowden
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors; D053823:Hedgehog Proteins / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology*; D016086:Lentivirus / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology* / Q000378:metabolism; D059008:Time-Lapse Imaging; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D007797:Laminin; D011509:Proteoglycans; C509239:SHH protein, human; D015534:Trans-Activators; C109288:cone rod homeobox protein; C059485:matrigel; D005346:Fibroblast Growth Factors; D003094:Collagen