Pluripotent Stem Cell Screening via Primitive Endoderm Gene Markers

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Solution Overview

Problem

Current methods for inducing differentiation of pluripotent stem cells into specific cells, such as myocardial or nerve cells, face variability in differentiation potency among donors and established strains, necessitating a more effective screening method to select high-potency stem cells for efficient production of differentiated cells.

Innovation Solution

Measuring the expression level of genes specific to primitive endoderm cells, like CER1, LEFTY1, LEFTY2, NODAL, and CXCR4, in pluripotent stem cells to identify and select those with lower expression levels, indicating higher differentiation potential into mesoderm or ectoderm-derived cells, thereby enhancing the efficiency of cell production and quality evaluation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If pluripotent stem cells are used for differentiation into specific cells, then various differentiated cells can be obtained, but the differentiation potency varies between donors and strains leading to inconsistent production efficiency

Engineering Contradiction:
Improvedifferentiation efficiencyVSAvoiddifferentiation potency consistency
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by measuring gene expression levels (such as CER1, LEFTY1, LEFTY2, NODAL, and CXCR4) before the differentiation process to identify and select pluripotent stem cells with high differentiation potency. This pre-screening approach allows researchers to choose cells that are most likely to differentiate efficiently into target cells, thereby improving both productivity and reliability of the differentiation process.

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If a screening method based on blood cell differentiation genes (TRIM58, CTSF, FAM19A5, TCERG1L) is used, then iPS cells with high blood cell differentiation potency can be selected, but methods for evaluating differentiation potency into other specific cells are required

Engineering Contradiction:
Improvescreening method applicabilityVSAvoidevaluation system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies universality by developing a screening method that uses genes expressed by primitive endoderm cells (CER1, LEFTY1, LEFTY2, NODAL, CXCR4) as indicators. These genes serve as universal markers that can predict differentiation potency into multiple cell types including myocardial cells, nerve cells, and other mesoderm or ectoderm-derived cells, making the screening method applicable across different differentiation targets rather than being limited to blood cell differentiation only.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Manufacturing precision

If stepwise differentiation with complicated culture conditions is used for a relatively long period, then differentiated cells can be obtained, but production time and process complexity increase

Engineering Contradiction:
Improvedifferentiation control precisionVSAvoiddifferentiation process time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-selecting pluripotent stem cells with high differentiation potency based on gene expression levels before initiating the differentiation process. This pre-selection ensures that the chosen cells will progress through the stepwise differentiation protocol more efficiently, reducing the overall time required while maintaining the necessary culture conditions and differentiation control precision.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by using gene expression levels (CER1, LEFTY1, LEFTY2, NODAL, CXCR4) as selection criteria to identify cells with optimal differentiation potential. By changing the selection parameter from random or morphology-based selection to gene expression-based selection, the process achieves faster and more reliable differentiation outcomes.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3950932B1Method for producing pluripotent stem cells capable of differentiating into specific cells, and application thereof
Publication Date: 2024.06.05 FUJIFILM CORP
  • EP3950932B1 patent drawingFigure 1
  • EP3950932B1 patent drawingFigure 2
  • EP3950932B1 patent drawingFigure 3~4

AI summary

An object of the present invention is to provide a producing method for a pluripotent stem cell capable of differentiating into a specific cell. According to the present invention, there is provided a producing method for a pluripotent stem cell capable of differentiating into a specific cell. According to the present invention, there is provided a pluripotent stem cell capable of differentiating into a specific cell. According to the present invention, there is provided a producing method for a differentiated cell, and a differentiated cell. According to the present invention, there is provided a method for quality evaluation of a pluripotent stem cell. Further, according to the present invention, there is provided a method of screening a pluripotent stem cell capable of differentiating into a specific cell.