mTOR Activator Enhances Somatic Cell Reprogramming Efficiency

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Solution Overview

Problem

Current methods for culturing human pluripotent stem cells are prone to contamination and economic inefficiencies due to reliance on animal-derived products, and the conditions for reprogramming somatic cells to induced pluripotent stem cells are not well-defined, particularly regarding mTOR activation and inhibition.

Innovation Solution

A composition and method utilizing an mTOR activator, such as 4,6-di-4-morpholinyl-N-(4-nitrophenyl)-1,3,5-triazin-2-amine, is used to enhance reprogramming efficiency by transducing reprogramming factors like OCT4, SOX2, and c-Myc into somatic cells, followed by treatment with the mTOR activator, which upregulates CXCR2 and cMYC, and decreases autophagy activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If animal-derived feeder cells or animal-derived gel coatings are used for culturing human pluripotent stem cells, then cell proliferation is supported, but contamination risk increases and safety concerns arise due to xenoprotein presence

Engineering Contradiction:

ImprovesafetyVSAvoidcontamination risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent removes animal-derived components (feeder cells and gel coatings) from the culturing system and replaces them with a defined chemically synthesized medium containing small molecule compounds. This extraction eliminates the source of xenoprotein contamination while maintaining cell proliferation support through alternative mechanisms.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses a defined chemically synthesized medium with small molecule compounds that can be easily prepared and discarded, replacing expensive and complex animal-derived products. This disposable medium system simplifies contamination control while supporting stem cell culture.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Productivity

If animal-derived special gels are used for stem cell culturing, then cell proliferation is maintained, but production cost increases making it unsuitable for mass production

Engineering Contradiction:

Improvemass production capabilityVSAvoidproduction cost

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The patent replaces expensive animal-derived special gels with a chemically synthesized medium containing small molecule compounds that are inexpensive to produce. This cost reduction enables scalable mass production of induced pluripotent stem cells while maintaining proliferation efficiency.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention changes the chemical composition parameters of the culturing medium from complex animal-derived substances to defined small molecule compounds. This parameter change simplifies the medium formulation, reduces cost, and enables consistent large-scale production.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If conventional reprogramming conditions are used without clear mTOR regulation, then reprogramming process can proceed, but reprogramming efficiency remains low due to undefined conditions

Engineering Contradiction:

Improvereprogramming efficiencyVSAvoidcondition definition clarity

Core Design Contradiction:

ProductivityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent optimizes specific parameters of the culturing medium by incorporating small molecule compounds that modulate mTOR signaling pathway. This parameter optimization creates clearly defined reprogramming conditions that significantly enhance reprogramming efficiency compared to conventional undefined conditions.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention introduces small molecule compounds as intermediaries that mediate mTOR pathway activation during reprogramming. These compounds serve as controllable mediators to achieve efficient reprogramming under clearly defined conditions, resolving the uncertainty of conventional methods.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 significantly increases reprogramming efficiency from somatic cells to induced pluripotent stem cells, making the process safer, more economically viable, and suitable for mass production by using a human placenta-derived cell conditioned medium.

Implementation Method 1

the mTOR activator upregulates the expression of CXCR2 and cMYC

Methodology Applied

Scientific EffectProtein expression upregulation:

Implementation Method 2

decreases autophagy activity

Methodology Applied

Scientific EffectAutophagy inhibition:

Data Source

PatentUS20230013363A1Composition for enhancing reprogramming efficiency from somatic cell to induced pluripotent stem cell, comprising mtor activator, and method for enhancing reprogramming efficiency by using same

Publication Date: 2023.01.19 KOREA UNIV RES & BUSINESS FOUND

AI summary

The present invention relates to a composition for enhancing reprogramming efficiency from somatic cells to induced pluripotent stem cells, comprising an mTOR activator, and a method for enhancing reprogramming efficiency by using same. In the method, reprogramming factors including OCT4, SOX2, c-Myc, and KLF4 are transduced into somatic cells, followed by treatment with an mTOR activator, thereby remarkably increasing reprogramming efficiency into induced pluripotent stem cells. Therefore, the composition and method can be used for effectively inducing the reprograming of somatic cells into induced pluripotent stem cells.