Pluripotent Cell Production Using Fermenting Bacteria

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Solution Overview

Problem

Embryonic stem cells and induced pluripotent stem cells pose ethical concerns and risk of canceration due to gene introduction methods, limiting their safety and applicability in regenerative medicine.

Innovation Solution

The method involves using bacteria with fermentation ability, such as lactic acid bacteria or Bacillus subtilis var. natto, to infect somatic cells, producing pluripotent cells without artificial gene introduction, thereby reducing canceration risk and ethical concerns.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If embryonic stem cells or induced pluripotent stem cells are used for regenerative medicine, then pluripotent cell production is achieved, but ethical concerns and canceration risk arise due to gene introduction methods

Engineering Contradiction:
Improvesafety of pluripotent cell productionVSAvoidcanceration risk and ethical concerns
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and eliminates the harmful c-Myc gene from the reprogramming factor combination, using only Oct3/4, Sox2, and Klf4. This removal of the cancer-associated gene directly reduces the canceration risk while maintaining the ability to generate pluripotent cells from somatic cells.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses small molecules or chemical compounds as intermediaries to facilitate the reprogramming process without requiring viral gene introduction. This intermediary approach allows transmission of reprogramming signals while avoiding the integration of foreign DNA into the host genome, thereby eliminating canceration risk.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If c-Myc gene is introduced into cells for iPS cell production, then pluripotent cell reprogramming is achieved, but canceration risk increases

Engineering Contradiction:
Improvereprogramming capabilityVSAvoidcanceration risk
Core Design Contradiction:
Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The invention extracts and eliminates the harmful c-Myc gene from the reprogramming factor combination, using only Oct3/4, Sox2, and Klf4. This removal of the cancer-associated gene directly reduces the canceration risk while maintaining the ability to generate pluripotent cells from somatic cells.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs transient expression systems where reprogramming factors are introduced temporarily without permanent genomic integration. The factors perform their reprogramming function and are then removed, leaving no persistent foreign genetic material that could cause canceration.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If adenovirus or plasmid vector is used for gene introduction, then iPS cell production safety is improved, but artificial forced expression of genes remains problematic

Engineering Contradiction:
Improveproduction safetyVSAvoidartificial gene introduction process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention replaces the mechanical/viral gene introduction system (adenovirus or plasmid vectors) with a chemical/small molecule-based system. This substitution eliminates the need for viral infection or transfection processes, simplifying the overall procedure while maintaining safety.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs cell-permeable small molecules that can enter cells autonomously without requiring external viral vectors or complex transfection machinery. The cells themselves take up the reprogramming factors through their natural membrane permeability mechanisms, eliminating the need for artificial gene introduction systems.

Inventive Principle:
Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach allows for the production of pluripotent cells that are safe for regenerative medicine applications, reducing the risk of canceration and addressing ethical concerns, and can be used for various disease treatments and anti-cancer research.

Implementation Method 1

bacteria having fermentation ability, such as lactic acid bacteria and Bacillus subtilis var. natto

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentEP2733204B1Method for producing pluripotent cell using bacterium having fermentation ability
Publication Date: 2024.11.06 INTEGRICULTURE INC
  • EP2733204B1 patent drawingFigure 1~2
  • EP2733204B1 patent drawingFigure 3
  • EP2733204B1 patent drawingFigure 4

AI summary

It is an object of the present invention to provide a method for producing pluripotent cells that are free of the risk of cellular canceration and that can be applied to regenerative medicine with a high degree of safety. The present invention provides a method for producing pluripotent cells from somatic cells comprising a step of bringing bacteria having fermentation ability or a component or secretory product thereof into contact with somatic cells.