Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors | Zendy

Anai Gonzalez-Cordero | Zendy; Kamil Kruczek | Zendy; Arifa Naeem | Zendy; Milan Fernando | Zendy; Magdalena Kloc | Zendy; Joana Ribeiro | Zendy; Debbie Goh | Zendy; Yanaí Durán | Zendy; Samuel J.I. Blackford | Zendy; Laura AbelleiraHervas | Zendy; Robert D. Sampson | Zendy; Ian O. Shum | Zendy; Matthew J. Branch | Zendy; Peter J. Gardner | Zendy; Jane C. Sowden | Zendy; James Bainbridge | Zendy; Alexander J. Smith | Zendy; Emma L. West | Zendy; R. A. Pearson | Zendy; Robin R. Ali | Zendy

Open Access

Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors

Author(s) -

Anai Gonzalez-Cordero,

Kamil Kruczek,

Arifa Naeem,

Milan Fernando,

Magdalena Kloc,

Joana Ribeiro,

Debbie Goh,

Yanaí Durán,

Samuel J.I. Blackford,

Laura AbelleiraHervas,

Robert D. Sampson,

Ian O. Shum,

Matthew J. Branch,

Peter J. Gardner,

Jane C. Sowden,

James Bainbridge,

Alexander J. Smith,

Emma L. West,

R. A. Pearson,

Robin R. Ali

Publication year - 2017

Publication title -

stem cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.207

H-Index - 76

ISSN - 2213-6711

DOI - 10.1016/j.stemcr.2017.07.022

Subject(s) - biology , transplantation , induced pluripotent stem cell , retina , retinal , stem cell , microbiology and biotechnology , retinal degeneration , anatomy , neuroscience , embryonic stem cell , genetics , botany , medicine , surgery , gene

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/medium cones survive and become incorporated within the adult mouse retina, supporting the potential of photoreceptor transplantation for treating retinal degeneration.

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