Journal
STEM CELLS
Volume 31, Issue 2, Pages 408-414Publisher
WILEY-BLACKWELL
DOI: 10.1002/stem.1268
Keywords
Embryonic; Induced pluripotent; Retina; Photoreceptors; Extracellular matrix; Three-dimensional culture
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Funding
- Medical Research Council U.K. [G03000341, G0901550 MR/J004553/1]
- Millers Trust
- Great Ormond Street Hospital Children's Charity
- Department of Health's National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital
- MRC [G0901550, MR/J004553/1, G0700438] Funding Source: UKRI
- Fight for Sight [1351/52] Funding Source: researchfish
- Great Ormond Street Hospital Childrens Charity [V1257, V1223, V1259] Funding Source: researchfish
- Medical Research Council [G0700438, MR/J004553/1, G0901550] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10001, NF-SI-0508-10130] Funding Source: researchfish
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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. STEM CELLS 2013;31:408-414
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