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

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

doi:10.1016/j.stemcr.2017.07.022

Stem Cell Reports (Sep 2017)

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

Anai Gonzalez-Cordero,
Kamil Kruczek,
Arifa Naeem,
Milan Fernando,
Magdalena Kloc,
Joana Ribeiro,
Debbie Goh,
Yanai Duran,
Samuel J.I. Blackford,
Laura Abelleira-Hervas,
Robert D. Sampson,
Ian O. Shum,
Matthew J. Branch,
Peter J. Gardner,
Jane C. Sowden,
James W.B. Bainbridge,
Alexander J. Smith,
Emma L. West,
Rachael A. Pearson,
Robin R. Ali

Affiliations

Anai Gonzalez-Cordero: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Kamil Kruczek: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Arifa Naeem: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Milan Fernando: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Magdalena Kloc: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Joana Ribeiro: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Debbie Goh: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Yanai Duran: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Samuel J.I. Blackford: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Laura Abelleira-Hervas: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Robert D. Sampson: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Ian O. Shum: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Matthew J. Branch: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Peter J. Gardner: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Jane C. Sowden: Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK
James W.B. Bainbridge: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Alexander J. Smith: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Emma L. West: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Rachael A. Pearson: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
Robin R. Ali: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK

DOI: https://doi.org/10.1016/j.stemcr.2017.07.022
Journal volume & issue: Vol. 9, no. 3
pp. 820 – 837

Abstract

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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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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