June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Expandable and Cryopreservable Retinal Progenitors: A new cell tool
Author Affiliations & Notes
  • Sacha Reichman
    Sorbonne Universite, Paris, Île-de-France, France
    INSERM, Paris, Île-de-France, France
  • Vivien Batoumeni
    Sorbonne Universite, Paris, Île-de-France, France
    Universite Paris-Saclay, Gif-sur-Yvette, Île-de-France, France
  • Tara Fournier
    Sorbonne Universite, Paris, Île-de-France, France
    Supbiotech, France
  • Céline Nanteau
    Sorbonne Universite, Paris, Île-de-France, France
  • Anais Potey
    Sorbonne Universite, Paris, Île-de-France, France
  • marilou clemencon
    Sorbonne Universite, Paris, Île-de-France, France
  • Gael Orieux
    Sorbonne Universite, Paris, Île-de-France, France
  • Jose Sahel
    Sorbonne Universite, Paris, Île-de-France, France
    INSERM, Paris, Île-de-France, France
  • Olivier Goureau
    INSERM, Paris, Île-de-France, France
  • Jerome E Roger
    Centre National de la Recherche Scientifique, Paris, Île-de-France, France
  • Sandy Gozlan
    Sorbonne Universite, Paris, Île-de-France, France
  • Footnotes
    Commercial Relationships   Sacha Reichman None; Vivien Batoumeni None; Tara Fournier None; Céline Nanteau None; Anais Potey None; marilou clemencon None; Gael Orieux None; Jose Sahel None; Olivier Goureau None; Jerome Roger None; Sandy Gozlan None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3850. doi:
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      Sacha Reichman, Vivien Batoumeni, Tara Fournier, Céline Nanteau, Anais Potey, marilou clemencon, Gael Orieux, Jose Sahel, Olivier Goureau, Jerome E Roger, Sandy Gozlan; Expandable and Cryopreservable Retinal Progenitors: A new cell tool. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3850.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Part of the challenge in cell therapy and drug discovery is the production of large number of identical cells. In this way, in 2014, we elaborated an innovative protocol for the production of self-forming retinal organoids (ROs) from human iPSCs. Initially composed by retinal progenitor cells (RPCs), ROs can be maintained in 3D cell cultures to generate all retinal cell types. The photoreceptor precursors present in structures represent the most appropriate population for cell replacement by transplantation approaches but also for disease modeling and screening test. However, the post-mitotic phenotype of this cell type limits its scalup production. To produce large quantity of photoreceptor precursors, we propose to isolate, expend and bank the RPCs present in ROs as a multipotent cell line.

Methods : Generation of floating ROs from native and fluorescent reporter hiPSC lines. Dissociation of young ROs and positive selection of the retinal progenitor cells (hiRPCs) using a new RPC-dedicated medium (RPCM) in adherent culture condition. Expansion and banking of hiRPCs. RNAseq analysis of hiRPCs generated. Use of cryopreserved hiRPCs for large retinal cells production.

Results : Development of the RPCM containing five specific molecules mimicking the early retinogenesis environment sustaining proliferation and multipotency. Thawed and passed hiRPCs maintained biochemical and transcriptional RPC phenotypes and their ability to differentiate into all retinal cell types. Depending on the media used, adherent cultures of hiRPCs generated retinal ganglion cells, amacrine cells, horizontal cell, bipolar and Müller glial cells but also RPE or mature photoreceptors. Development of robust conditions produced large cultures of photoreceptor precursors enriched up to 90% within a few weeks and without a purification step. Innovative combination of RNA-seq analysis between hiRPCs and ROs identified new candidate genes involved in developmental or degenerative retinal diseases.

Conclusions : All retinal cell types can be generated from banked hiRPCs. Large-scale productions of relevant human retinal cells, such as hiRPCs and photoreceptor precursors, are now available. The hiRPCs and derived retinal cells may offer new biological tools to better understand retinal degenerative diseases and develop cellular and drug-based therapies

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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