期刊
STEM CELL REPORTS
卷 9, 期 3, 页码 820-837出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2017.07.022
关键词
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资金
- Medical Research Council UK [MR/J004553/1, MR/M007871/1, MR/L012758/1]
- European Research Council [ERC-2012-ADG_20120314]
- Fight for Sight [1448/1449]
- Macular Vision Research Foundation
- Miller's Trust
- Moorfields Eye Charity
- Alcon Research Institute
- Department of Health's NIH Research Biomedical Research Center at Moorfields Eye Hospital
- MRC [G0700089]
- Wellcome Trust [GR082557, 099173/Z/12/Z]
- MRC [G0700089, MC_PC_15004, MR/M015688/1, MR/L012758/1, MR/J004553/1, MR/M007871/1] Funding Source: UKRI
- Fight for Sight [1448/49, 1351/52] Funding Source: researchfish
- Great Ormond Street Hospital Childrens Charity [V2816] Funding Source: researchfish
- Medical Research Council [MR/M007871/1, MC_PC_15004, MR/L012758/1, MR/M015688/1, MR/J004553/1, G0700089] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10074, NF-SI-0515-10069, NF-SI-0508-10130, NIHR-RP-011-003] Funding Source: researchfish
- Rosetrees Trust [M257] Funding Source: researchfish
Transplantation of rod photoreceptors, derived either from neonatal retinae or pluripotent stem cells (PSCs), can restore rod-mediated visual function in murine models of inherited blindness. However, humans depend more upon cone photoreceptors that are required for daylight, color, and high-acuity vision. Indeed, macular retinopathies involving loss of cones are leading causes of blindness. An essential step for developing stem cell-based therapies for maculopathies is the ability to generate transplantable human cones from renewable sources. Here, we report a modified 2D/3D protocol for generating hPSC-derived neural retinal vesicles with well-formed ONL-like structures containing cones and rods bearing inner segments and connecting cilia, nascent outer segments, and presynaptic structures. This differentiation system recapitulates human photoreceptor development, allowing the isolation and transplantation of a pure population of stage-matched cones. Purified human long/mediumcones survive and become incorporated within the adult mouse retina, supporting the potential of photoreceptor transplantation for treating retinal degeneration.
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