Desulphated GAG Culture Medium for Stem Cell Expansion

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Solution Overview

Problem

Stem cells are present in limited quantities and are difficult to expand and differentiate, especially from postembryonic sources, due to their location in hard-to-reach organs and ethical concerns surrounding embryonic stem cell harvesting.

Innovation Solution

A medium comprising desulphated Glycosaminoglycan (GAG) or low molecular weight heparin, combined with specific cytokines, is used to culture and differentiate stem cells into target effector cells, allowing for the expansion and generation of primitive lineage-specific progenitor cells with self-renewal and functional maturation capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If stem cells are expanded in culture, then the quantity of stem cells increases, but the cells tend to differentiate into less potent descendants

Engineering Contradiction:
Improvequantity of stem cellsVSAvoidpotency of stem cells
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical parameters of the culture medium by adding desulphated Glycosaminoglycan (GAG) at concentrations of 0.1-100 mg/l, which modifies the biochemical environment to maintain stem cell potency during expansion. This parameter change prevents differentiation while allowing proliferation, resolving the contradiction between increasing quantity and maintaining composition stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Desulphated GAG acts as an intermediary substance in the culture medium that mediates between the stem cells and the differentiation-inducing signals in the environment. It binds to and neutralizes differentiation signals, allowing stem cells to proliferate while maintaining their undifferentiated state and potency.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If embryonic stem cells are harvested, then sufficient quantities can be obtained, but ethical concerns arise

Engineering Contradiction:
Improvequantity of stem cellsVSAvoidethical concerns
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses postembryonic stem cells from umbilical cord blood, which are readily available and can be obtained without ethical concerns. These cells serve as a disposable, ethically acceptable alternative to embryonic stem cells, providing sufficient quantities for research and therapy without harming embryos or raising moral objections.

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

Solution Approach 2:

The patent extracts stem cells from an alternative source (umbilical cord blood) rather than from embryos. This extraction from a non-controversial source provides the necessary cell quantities while avoiding the ethical problems associated with embryonic stem cell harvesting.

Inventive Principle:
Principle #2Taking out (Extraction)

3Object-affected harmful factors

If stem cells are obtained from postembryonic sources, then ethical concerns are avoided, but the cells are present in limited quantities and difficult to reach

Engineering Contradiction:
Improveethical concernsVSAvoidquantity of stem cells
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent applies preliminary expansion culture to the harvested postembryonic stem cells before transplantation. By pre-expanding the cells in culture with optimized medium containing desulphated GAG, small initial samples from umbilical cord blood can be multiplied into sufficient quantities for clinical therapy, solving the quantity limitation while maintaining ethical advantages.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the culture conditions by adding desulphated Glycosaminoglycan to the expansion medium, which transforms the growth characteristics of postembryonic stem cells. This parameter change enables robust proliferation of cells from limited postembryonic sources, converting scarce starting material into sufficient therapeutic quantities.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2142642B1Methods and means for stem cell proliferation and subsequent generation and expansion of progenitor cells, as well as production of effector cells as clinical therapeutics
Publication Date: 2017.08.09 IPD THERAPEUTICS
  • EP2142642B1 patent drawingFigure 1
  • EP2142642B1 patent drawingFigure 2~3
  • EP2142642B1 patent drawingFigure 4~5

AI summary

The invention is related to methods for expanding and differentiating hemopoietic progenitor cells in a medium comprising a collection of cytokines, desulphated glycosaminoglycan and human serum. The invention further relates to a collection of cells obtainable by a method of the invention, use of the collection of cells, and a kit of parts for expanding and differentiating hemopoietic progenitor cells.