Ciliary Marginal Zone-Like Structure Formation for Pure Neural Retina

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Solution Overview

Problem

There is no known method for producing a ciliary marginal zone-like structure from pluripotent stem cells with high efficiency.

Innovation Solution

A method involving the formation of a cell aggregate comprising a ciliary marginal zone-like structure, retinal pigment epithelium, and neural retina, where the neural retina is present on the surface and forms a continuous, stratified layer, allowing for the production of a highly pure neural retina by cutting it out from the aggregate.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods are used to produce ciliary marginal zone-like structure from pluripotent stem cells, then the structure can be formed, but the production efficiency is low

Engineering Contradiction:
Improveproduction efficiency of ciliary marginal zone-like structureVSAvoidtime required for structure formation
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The invention applies preliminary action by pre-forming cell aggregates with specific compositions containing pluripotent stem cells, Fezf2-expressing cells, and Chx10-expressing cells before initiating the differentiation process. This pre-organization of cell types and their spatial arrangement accelerates subsequent development into ciliary marginal zone-like structures, reducing overall production time while maintaining high efficiency

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If the neural retina is present on the surface of the cell aggregate, then it forms a continuous stratified layer, but the complexity of isolating pure neural retina increases

Engineering Contradiction:
Improvecontinuity and stratification of neural retinaVSAvoidcomplexity of isolation process
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention applies the extraction principle by isolating the neural retina from the surface of the cell aggregate through a simple mechanical cutting or detachment process. The neural retina, being positioned on the surface as a continuous stratified layer, can be easily separated from the underlying cell aggregate, yielding highly pure neural retina tissue without requiring complex isolation procedures

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP3842524B1Method for producing ciliary marginal zone-like structure
Publication Date: 2025.12.24 SUMITOMO CHEM CO LTD
  • EP3842524B1 patent drawingFigure 1~2
  • EP3842524B1 patent drawingFigure 3~4
  • EP3842524B1 patent drawingFigure 5~6

AI summary

The present invention provides a method for producing a cell aggregate containing a ciliary marginal zone-like structure, including a step of culturing a cell aggregate containing a retinal tissue in which Chx10 positive cells are present in a proportion of 20% or more of the tissue in a serum-free medium or serum-containing medium each containing a substance acting on the Wnt signal pathway for only a period before the appearance of a RPE65 gene expressing cell, followed by culturing the "cell aggregate in which a RPE65 gene expressing cell does not appear" thus obtained in a serum-free medium or serum-containing medium each not containing a substance acting on the Wnt signal pathway and so on. According to the present invention, a ciliary marginal zone-like structure can be produced with high efficiency.