Retinal development and repair: use of pluripotent stem cells

Team leader: Olivier Goureau

Introduction

We are working on cell therapy using the implantation of stem cell-derived retinal cells. This constitutes a therapeutic option for the treatment of retinal degenerative diseases, affecting photoreceptors and retinal pigment epithelial cells.

Presentation

Inherited and acquired degenerative diseases of the retina are a significant cause of incurable vision loss worldwide. Rescuing the degenerated retina is a major challenge for which specific cell replacement is one of the most promising approaches. Our laboratory utilizes human induced pluripotent stem (iPS) cell technology to generate different retinal cell types for cell-based rescue or replacement strategies and for use in human retinal disease modeling. To meet these goals, we followed different objectives:

Generation human fluorescent reporter iPS cell lines to probe retinal differentiation process ;
Development of innovative and robust protocols allowing the differentiation of human iPS cells into different retinal cell types (retinal ganglion cells, photoreceptors and RPE cells) ;
Derivation of iPS cells from patients affected by specific inherited retinal dystrophies to understand retinal pathological mechanisms and to further develop large-scale drug screening.

Research areas

Pluripotent stem cells
Retinal development
Retinal degeneration
Cell therapy

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Publications

Updated and complete list by scientist
Visiting the ORCID links you will find the updated publications list for the following scientists:
- Olivier Goureau [>>]
- Gaël Orieux [>>]
2020

Dynamic full-field optical coherence tomography : 3D live-imaging of retinal organoids
Scholler J, Groux K, Goureau O, Sahel J-A, Fink M, Reichman S, Boccara C and Grieve K. Light Sci. Appl. 2020 Aug 17;9:140.

Generation and characterization of transplantable population of human iPSC-derived retinal ganglion cells.Generation and characterization of transplantable population of human iPSC-derived retinal ganglion cells.
Rabesandratana O, Chaffiol A, Mialot A, Slembrouck-Brec A, Joffrois C, Nanteau C, Rodrigues A, Gagliardi G, Reichman S, Sahel JA, Chedotal A, Duebel J, Goureau O and Orieux G. Frontiers Cell Dev. Biol. Oct 27;8:585675.

SARS-CoV-2 targets neurons of 3D human brain organoids
Anand Ramani et Müller L, Niklas Ostermann P, Gabriel E, Abida-Islam P, Müller-Schiffmann A, Mariappan A, Goureau O, Gruell H, Walker A, Andrée M, Hauka S, Houwaart T, Dilthey A, Wohlgemuth K, Omran H, Klein F, Wieczorek D, Adams O, Timm J, Korth C, Schaal H, Gopalakrishnan J.
EMBO J (2020)e106230 https://doi.org/10.15252/embj.2020106230

Clinical-grade production and safe delivery of human ESC derived RPE sheets in primates and rodents.
Ben M'Barek K, Bertin S, Brazhnikova E, Jaillard C, Habeler W, Plancheron A, Fovet CM, Demilly J, Jarraya M, Bejanariu A, Sahel JA, Peschanski M, Goureau O,CA and Monville C,CA. Biomaterials 2020, 230:119603.

AAV-mediated gene delivery to 3D retinal organoids derived from human induced pluripotent stem cells.AAV-mediated gene delivery to 3D retinal organoids derived from human induced pluripotent stem cells.
Garita-Hernandez M, Routet F, Guibbal L, Khabou H, Toualb L, Riancho L, Reichman S, Duebel J, Sahel JA, Goureau O and Dalkara D. Int J Mol Sci. 2020, Feb 3;21(3).

Nouvelle approche thérapeutique pour les rétinites pigmentaires : la transplantation de photorécepteurs dérivées de cellules souches.
Goureau O et Orieux G. Médecine/Science 2020 36, 600-606.

Les organoïdes de rétine : un nouvel outil pour la compréhension et le traitement des pathologies rétiniennes
Goureau O, Reichman S et Orieux G. Médecine/Science 2020, 36, 626-632.
2019

The primate model for understanding and restoring vision.
Picaud S, Dalkara D, Marazova K, Goureau O, Roska B and Sahel J-A. Proc. Natl. Acad. Sci. USA 2019 116(52),26280-26287.

Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach.
Gagliardi G, Ben M’Barek K and Goureau O
Prog Retin Eye Res. 2019. 71,1-25.

Generation of human induced pluripotent stem cell lines from a patient with ITM2B-related retinal dystrophy and a non-mutated brother
Wohlschlegel J, Letellier C, Liu B, Méjécase , Slembrouck-Brec A2, Condroyer C, Michiels C, Sahel JA, Reichman S, Zeitz C, Goureau O and Audo I
Stem Cell Res. 2019, Nov 5;41:101625.

Clinical-grade production and safe delivery of human ESC derived RPE sheets in primates and rodents.
Ben M'Barek K, Bertin S, Brazhnikova E, Jaillard C, Habeler W, Plancheron A, Fovet CM, Demilly J, Jarraya M, Bejanariu A, Sahel JA, Peschanski M, Goureau O and Monville C.
Biomaterials 2019 Nov 6:119603.

Restoration of visual function by transplantation of optogenetically engineered photoreceptors.
Garita-Hernandez M, Lampic M, Chaffiol A, Guibbal L, Routet F, Santos-Ferreira T, Gasparini S, Borsch O, Gagliardi G, Reichman S, Picaud S, Sahel J-A, Goureau O, Ader M, Duebel J and Dalkara D
Nat Comm 2019 Oct 4;10(1):4524.

Reprogramming of adult retinal Müller glial cells into human induced pluripotent stem cells as an efficient source of retinal cells
Slembrouck-Brec A, Rodrigues A, Rabesandratana O, Gagliardi G, Nanteau C, Fouquet S, Thuret G, Reichman S, Orieux G and Goureau O
Stem Cell Int. 2019 2019 Jul 15;2019:7858796
2018

Characterization and transplantation of CD73-positive photoreceptors isolated from human iPSC-derived retinal organoids.
Gagliardi G, Ben M'Barek K, Chaffiol A, Slembrouck-Brec A, Conart JB, Nanteau C, Rabesandratana O, Sahel J-A, Duebel J, Orieux G, Reichman S, and Goureau O.
Stem Cell Rep. 2018, 11(3):665-680.

Defined Xeno-free and Feeder-free culture conditions for the generation of human iPSC-derived retinal cell models.
Slembrouck-Brec A, Nanteau C, Sahel J-A, Goureau O and Reichman S.
J. Vis. Exp. 2018, Sep 6;(139).

Engineering transplantation-suitable retinal pigmented epithelium tissue derived from human embryonic stem cells.
Ben M'Barek K, Habeler W, Plancheron A, Jarraya M, Goureau O and Monville C.
J. Vis. Exp. 2018, Sep 6;(139).

Pluripotent stem cell-based approaches to explore and treat optic neuropathies.
Rabesandratana O, Goureau O and Orieux G.
rontiers in Neuroscience 2018, Sep 20;12:651.

Optogenetic light sensors in human retinal organoids
Garita-Hernandez M, Guibbal L, Toualb L, Routet F, Chaffiol A, Winckler C, Harinquet M, Robert C, Fouquet S, Bellow S, Sahel J-A, Goureau O, Duebel J and Dalkara D.
Frontiers in Neuroscience 2018, Nov 02;12:789.

Non-invasive gene delivery to foveal cones for gene therapy and vision restoration.
Khabou H, Garita M, Chaffiol A Reichman S, Jaillard C, Brazhnikova E, Bertin S, Fradot V, Desrosiers M, Winckler C, Goureau O, Picaud S, Duebel J, Sahel J-A, and Dalkara D.
J. Clin. Invest. Insight 2018, Jan 25;3(2)
2017

Human ESC-derived retinal epithelial cell sheets potentiate rescue of photoreceptor cell loss in rats with retinal degeneration.
Ben M'Barek K, Habeler W, Plancheron A, Jarraya M, Regent F, Terray A, Yang Y, Chatrousse L, Domingues S, Masson Y, Sahel JA, Peschanski M, Goureau O and Monville C.
Sci. Transl Med. 2017, Dec 20;9(421).

Activated monocytes resist elimination by retinal pigment epithelium and downregulate their OTX2 expression via TNFα.
Mathis T, Housset M, Eandi C, Beguier F, Touhami S, Reichman S, Augustin S, Gondouin P, Sahel J-A, Kodjikian L, Goureau O, Guillonneau X and Sennlaub F. Aging Cell 2017, 16(1):173-182.

Generation of storable retinal organoids and retinal pigmented epithelium from adherent human iPS cells in xeno-free and feeder-free conditions.
Reichman S, Slembrouck A, Gagliardi G, Chaffiol A, Terray A, Nanteau C, Potey A, Belle M, Rabesandratana O, Duebel J, Orieux G, Nandrot EF, Sahel J-A and Goureau O. Stem Cells 2017, 35(5):1176-1188.

Generation of an induced pluripotent stem cell line from a patient with autosomal dominant retinitis pigmentosa due to a mutation in the NR2E3 gene.
Terray A, Slembrouck A, Nanteau C, Condroyer C, Zeitz C, Sahel J-A, Audo I, Reichman S, and Goureau O. Stem Cell Research 2017, 24:1-4.

Otx2-genetically modified retinal pigment epithelial cells rescue photoreceptors after transplantation.
Kole C, Klipfel L, Yang Y, Ferracane V, Blond F, Reichman S, Millet-Puel G, Clérin E, Aït-Ali N, Pagan D, Camara H, Delyfer MN, Nandrot E, Sahel JA, Goureau O and Léveillard T. Mol. Therapy 2017 [Sep 8. pii: S1525-0016(17)30419-7].

Establishment of an induced pluripotent stem (iPS) cell line from dermal fibroblasts of an asymptomatic patient with dominant PRPF31 mutation.
Terray A, Fort V, Slembrouck A, Nanteau C, Sahel J-A, Reichman S, Audo I and Goureau O. Stem Cell Research 2017, 25:26-29.

Further insights into the ciliary gene and protein KIZ and its murine ortholog PLK1S1 mutated in rod-cone dystrophy.
El Shamieh S, Méjécasse C, Bertelli M, Terray A, Michiels C, Condroyer C, Fouquet S, Sadoun M, Clérin E, Liu B, Léveillard T, Goureau O, Sahel J-A, Audo I, Zeitz C. Genes 2017, Oct 18; 8(10), 277.
2016

Let there be light: gene and cell therapy for blindness.
Dalkara D, Goureau O, Marazova K and Sahel J-A.
Hum. Gene Ther. 2016 2,134-147.

Gene and cell therapy for inherited retinal dystrophies
Garita-Hernandez M, Goureau O, Dalkara D. (August 2016).
In: eLS. John Wiley & Sons Ltd: Chichester. DOI: 10.1002/9780470015902.a0026565.

Production of retinal cells from confluent human iPS cells.
Reichman S and Goureau O.
Methods Mol Biol. 2016 1357:339-351.
2015

The protein tyrosine phosphatase interacting protein 51 (PTPIP51) is required for the differentiation of photoreceptors.
Orieux G, Slembrouck A, Bensaïd M, Sahel JA and Goureau O.
Neuroscience. 2015, 300, 276-285
2014

Production of in vitro retina from pluripotent human stem cells: a new therapeutic tool.
Reichman S, Sahel JA, Goureau O.
Med Sci (Paris). 2014 Oct;30(10):845-8. doi: 10.1051/medsci/20143010009. Epub 2014 Oct 14. French. No abstract available.

From confluent human iPS cells to self-forming neural retina and retinal pigmented epithel
Reichman S, Terray A, Slembrouck A, Nanteau C, Orieux G, Habeler W, Nandrot EF, Sahel JA, Monville C, Goureau O.
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8518-23. doi: 10.1073/pnas.1324212111.

El Shamieh S, Neuillé M, Terray A, Orhan E, Condroyer C, Démontant V, Michiels C, Antonio A, Lancelot ME, Letexier M, Saraiva JP, Léveillard T, Mohand-Saïd S, Goureau O, Sahel J-A, Zeitz C, Audo J.
Whole exome sequencing identifies PLK1S1 as a new ciliary gene underlying autosomal recessive rod-cone dystrophy.
Am J Hum Genet. 2014 94(4):625-633.

Orieux G, Picault L, Slembrouck A, Roger JE, Guillonneau X, Sahel J-A, Saule S, McPherson JP, Goureau O. Involvement of Bcl-2-associated transcription factor 1 in the differentiation of early-born retinal cells. J. Neurosci. 2014 34(4): 1530-1541.

Audo I, Bujakowska K, Orhan E, El Shamieh S, Sennlaub F, Guillonneau X, Antonio A, Michiels C Lancelot M-E, Letexier M, SaraivaJ-P, Nguyen H, Luu TD, Léveillard T, Poch O, Dollfus H, Paques M, Goureau O, Mohand-Saïd S, Bhattacharya SS, Sahel J-A, Zeitz C. The familial dementia gene revisited: a missense mutation revealed by whole exome sequencing identifies ITM2B as a candidate gene underlying a novel autosomal dominant retinal dystrophy in a large family. Hum Mol Genet. 2014 23(2): 491-501.
2013

Brevet Européen - N°EP13165654.8 (26/04/2013) Reichman S., Goureau, O., Sahel J-A. METHODS FOR OBTAINING RETINAL PROGENITORS, RETINAL PIGMENTED EPITHELIAL CELLS AND NEURAL RETINAL CELLS.

Lustremant C, Habeler W, Plancheron A, Goureau O, Grenot L, de la Grange P, Audo I, Nandrot E, Monville C. Human induced pluripotent stem cells as a tool to model a form of Leber congenital amaurosis.Cell. Reprogramming 2013, 15(3): 233-246.
2012

Laurent M, Le Dréau G, Guillonneau X, Lelièvre E, Slembrouck A, Goureau O, Martinerie C, Marx M. Temporal and spatial expression of CCN3 during retina development. Dev Neurobiol. 2012, 72(11): 1363–1375.

Lelièvre EC, Benayoun BA, Mahieu L, Roger JE, Sahel JA, Sennlaub F, Veitia RA, Goureau O, Guillonneau X. A regulatory domain is required for Foxn4 activity during retinogenesis. J Mol Neurosci.2012, 46(2): 315-32