Rejuvenating Aged Mesenchymal Stem Cells via Culture Medium Composition

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Solution Overview

Problem

Aged mesenchymal stem cells collected from human tissue have low therapeutic efficiency due to low proliferation and differentiation abilities, and there is a lack of methods to rejuvenate them to have characteristics similar to those of young stem cells.

Innovation Solution

A medium composition containing FBS, selenium, EGF, bFGF, and NAC is used to culture mesenchymal stem cells, which includes optional insulin or hydrocortisone, to rejuvenate aged stem cells by enhancing their proliferation, telomerase activity, and pluripotency, making them similar to young stem cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If mesenchymal stem cells are collected from aged persons, then the cells can be obtained for therapy, but their proliferation and differentiation abilities are low

Engineering Contradiction:
Improveproliferation abilityVSAvoidtherapeutic efficiency
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the chemical parameters of the culture medium by adding specific antioxidants (NAC, ascorbic acid, selenium) and growth factors (bFGF, EGF, insulin) to reverse the aged state of stem cells. This parameter change in the medium composition restores cellular functions including proliferation and differentiation abilities, transforming aged stem cells into a younger functional state with improved therapeutic efficiency

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses antioxidants and growth factors as intermediary substances that mediate between the aged stem cells and their desired rejuvenated state. These intermediaries (NAC, ascorbic acid, bFGF, EGF) act as signaling molecules and protective agents that facilitate cellular rejuvenation by reducing oxidative stress and activating proliferation pathways

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If mesenchymal stem cells are cultured in vitro for long term, then more cells can be obtained, but environmental stress accumulates causing senescence

Engineering Contradiction:
Improvecell numberVSAvoidcellular senescence
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by adding antioxidants and growth factors to the culture medium before senescence fully develops. This preventive approach addresses environmental stress accumulation proactively, maintaining cellular stability and preventing senescence onset during long-term culture, thereby preserving therapeutic quality while expanding cell numbers

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent converts the harmful effect of environmental stress and oxidative stress into a beneficial outcome by using antioxidants. The same environmental conditions that would normally cause senescence are transformed into opportunities for cellular rejuvenation through the addition of NAC, ascorbic acid, and selenium, which neutralize stress and promote cell health

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Ease of manufacture

If conventional culture medium is used, then culture process is simple, but stem cells show low telomerase activity and pluripotency

Engineering Contradiction:
Improveculture process simplicityVSAvoidpluripotency
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent modifies the chemical composition parameters of the conventional culture medium by incorporating specific concentrations of antioxidants (NAC 1-10 μM, ascorbic acid 10-100 μM, selenium 0.1-1 μM) and growth factors (bFGF 1-10 ng/ml, EGF 1-10 ng/ml, insulin 1-10 μg/ml). These parameter changes maintain ease of culture while dramatically improving telomerase activity and pluripotency, achieving both simplicity and effectiveness

Inventive Principle:
Principle #35Parameter changes

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

The medium composition effectively rejuvenates aged mesenchymal stem cells, increasing their proliferation rate, telomerase activity, and pluripotency, thereby enhancing their therapeutic potential and efficacy in cell therapy.

Implementation Method 1

when mesenchymal stem cells collected from the adipose tissue isolated from an aged patient are cultured in a medium containing an antioxidant and a growth factor

Methodology Applied
Scientific EffectAntioxidant: Oxidation

Implementation Method 2

the medium composition containing FBS (fetal bovine serum), 0.5∼1 ng/ml selenium

Methodology Applied
Scientific EffectAntioxidant: Oxidation

Implementation Method 3

1∼100 ng/ml bFGF (basic fibroblast growth factor)

Methodology Applied
Scientific EffectGrowth factor signaling:

Implementation Method 4

10∼50 ng/ml EGF (epidermal growth factor)

Methodology Applied
Scientific EffectGrowth factor signaling:

Data Source

PatentEP2811015B1Culture-medium composition for rejuvenating stem cells
Publication Date: 2020.09.02 R BIO CO LTD
  • EP2811015B1 patent drawingFigure 1A~1B
  • EP2811015B1 patent drawingFigure 2A~2B
  • EP2811015B1 patent drawingFigure 3

AI summary

The present invention relates to a medium composition for transforming stem cells from an aged person into young stem cells, and more particularly to a medium composition for culturing stem cells, which is used to rejuvenate stem cells from an aged person so as to have characteristics similar to those of the stem cells of young people, and to a method for rejuvenating stem cells, which comprises culturing stem cells from an aged person in the medium composition. According to the present invention, even mesenchymal stem cells collected from over 60 years old patients can be transformed into young mesenchymal stem cells having high differentiation ability, high telomerase activity, and high ability to express stem cell markers. Thus, the present invention can significantly increase the efficacy of cell therapy employing mesenchymal stem cells.