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Generation of retinal cells from human iPS cells-MA0002

Market challenges

Human induced pluripotent stem (hiPS) cells could be used as an unlimited source of retinal cells for the treatment of retinal degenerative diseases. Moreover, different field of application establishes potential roles for iPSCs in modeling diseases and drug screening. Although much progress has been made in the differentiation of pluripotent stem cells towards different retinal lineages, the production of retinal cells from hiPS cells for therapeutic approaches require the development of easy and standardized protocols.

Innovative solution

To address these requirements, Dr. Olivier Goureau’s team, at the Vision Institute, developed a new, simple and effective retinal differentiation protocol of hiPS cells bypassing embryoid body formation and the use of exogenous molecules and substrates. In 2 weeks, confluent hiPS cells cultured in pro-neural medium can generate both retinal pigmented epithelial (RPE) cells and self-forming neural retina-like structures containing retinal progenitor cells. These progenitors can be differentiated into all retinal cell types, including retinal ganglion cells and precursors of photoreceptors.

Suggested applications

• Drug discovery (phenotype and target based high thoughput screening of pharmacological compounds, in vitro models of human retinal degenerative diseases...)
• Retinal cell therapy (treatment of AMD, retinitis pigmentosa...)
• Research tool (in vitro model of human retinal development and disease)

Development status

The identification of each retinal cell type was based on the presence of typical biomarker (immunohistochemistry). Their functionality was validated in vitro (phagocytosis test).
The high throughput screening protocol (384 well plates) with RPE cells generated with this new method is now running and transposable to another HTS device.
In vivo experiments (in rats) to validate the efficacy of these differentiated cells (RPE and photoreceptor precursors) in cell therapy are ongoing.

Competitive advantages

• Easy and rapid differentiation method (Generation of multipotent human retinal progenitor cells in 14 days)
• Generation of all retinal cell types
• Process not depending on the iPS clone, or the reprogrammation method used
• Readily efficient, scalable (treatment of the NR-like structures to promote one specific retinal cell type) and GMP-like protocol compatible with the production of retinal cells for regenerative medicine
• Patent application filed in 2013 and 2017 (USA, Canada, EU, Australia, India, Japan, Israel, China, Korea)
• Secret konw-how

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