Ecklonia cava extract reprograms adipose stem cells

Solution Overview

Problem

Current methods for generating induced pluripotent stem cells, such as fusion with ES cells, somatic cell nuclear transfer, and reprogramming by gene factors, face issues like cell stability, high ova requirement, low efficiency, and cancer risk, particularly when using virus-mediated approaches, limiting the production of safe and efficient cell therapeutic agents.

Innovation Solution

Incorporating Ecklonia cava extract in a cell culture medium at concentrations of 10 to 400 µg/ml to reprogram adipose-derived mesenchymal stem cells into induced pluripotent stem cells, utilizing a medium composition that includes Dulbecco's modified eagle's medium or other variants, with optional addition of energy water and specific oxides, to enhance reprogramming efficiency and safety.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If reprogramming by gene factor method using virus is used, then reprogramming efficiency is improved, but cancer risk increases and safety deteriorates

Engineering Contradiction:
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent extracts and removes the harmful viral vector component from the reprogramming process while retaining the beneficial reprogramming function. Instead of using virus-mediated delivery of reprogramming factors, the invention uses direct introduction of reprogramming genes (Oct4, Sox2, Klf4, c-Myc) into adipose-derived stem cells through transfection methods, thereby eliminating cancer risk associated with viral integration while maintaining reprogramming efficiency

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the harmful effect of viral vectors (which can cause cancer through random integration) into a beneficial approach by using non-viral transfection methods. The reprogramming factors are delivered without the carcinogenic risks of viral integration, thus transforming a harmful delivery mechanism into a safe one while achieving the same reprogramming outcome

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

2Adaptability or versatility

If fusion with ES cell method is used, then pluripotent stem cells are obtained, but cell stability deteriorates due to additional genes

Engineering Contradiction:
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent extracts only the necessary reprogramming function from the ES cell fusion method without incorporating the harmful aspect of additional chromosome pairs. By directly introducing specific reprogramming genes (Oct4, Sox2, Klf4, c-Myc) into adipose-derived stem cells, the invention achieves pluripotent stem cell generation without the genetic instability caused by ES cell fusion

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the reprogramming process into specific gene delivery (Oct4, Sox2, Klf4, c-Myc) rather than whole ES cell fusion. This segmentation allows precise control over which genetic elements are introduced, avoiding the addition of entire chromosome pairs and associated instability while maintaining the essential reprogramming function

Inventive Principle:
Principle #1Segmentation

3Adaptability or versatility

If somatic cell nuclear transfer method is used, then pluripotent stem cells are obtained, but productivity decreases due to high ova requirement and low efficiency

Engineering Contradiction:
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent enables adipose-derived stem cells to self-reprogram into pluripotent stem cells through direct gene transfection, eliminating the need for external ova or complex nuclear transfer procedures. The cells undergo autonomous reprogramming by expressing introduced reprogramming factors, dramatically simplifying the process and eliminating the bottleneck of ova availability

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent inverts the traditional approach by instead of transferring nuclei into ova, directly introducing reprogramming genes into the somatic cells themselves. This reversal of the nuclear transfer concept achieves the same end result (pluripotent stem cells) but with vastly improved efficiency and without requiring ova

Inventive Principle:
Principle #13The other way round (Inversion)

4Productivity

If embryonic stem cells are used, then excellent cell proliferation and potency are achieved, but ethical issues arise

Engineering Contradiction:
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent creates induced pluripotent stem cells that copy the essential properties of embryonic stem cells (pluripotency, self-renewal capacity, differentiation potential) without using actual embryonic cells. By reprogramming adult adipose-derived stem cells to express embryonic stem cell markers (Oct4, Sox2, Nanog), the invention produces functional equivalents that eliminate ethical concerns while maintaining excellent proliferation and potency

Inventive Principle:
Principle #26Copying

Data Source

PatentEP3156481B1Method for manufacturing induced pluripotent stem cells from adipose-derived mesenchymal stem cells and induced pluripotent stem cells manufactured by same method
Publication Date: 2024.04.03
  • EP3156481B1 patent drawingFigure 1~3
  • EP3156481B1 patent drawingFigure 4~5
  • EP3156481B1 patent drawingFigure 6~7

AI summary

The present disclosure relates to a medium composition for reprogramming induced pluripotent stem cells, containing an Ecklonia cava extract. Also, the present disclosure relates to a method for manufacturing induced pluripotent stem cells by using the medium composition. When the medium composition according to the present disclosure is used, induced pluripotent stem cells can be efficiently produced using adipose-derived mesenchymal stem cells safely and easily. The manufactured pluripotent stem cells are differentiable into various cells, and thus can be favorably used as a cell therapeutic agent.