Osteogenic Differentiation Using FGF and TGFB Growth Factors

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Solution Overview

Problem

Current methods for osteogenic differentiation of bone marrow stem cells and mesenchymal stem cells are inefficient, leading to a significant proportion of transplanted cells not contributing to bone tissue formation, and the quantity of these cells is often insufficient, especially in conditions like glucocorticoid use or genetic disorders.

Innovation Solution

Culturing bone marrow stem cells and mesenchymal stem cells in the presence of serum or plasma, fibroblast growth factor (FGF), and transforming growth factor beta (TGFB) to enhance osteogenic differentiation, resulting in increased quantities of osteoprogenitor and osteoblast phenotype cells with reduced HLA-DR expression for improved immunoprivilege.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If stem cells are transplanted without osteogenic differentiation, then the cells retain multipotency, but a considerable proportion of transplanted cells do not contribute to bone tissue formation

Engineering Contradiction:

Improvebone tissue formation efficiencyVSAvoidcell commitment to osteogenic lineage

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by differentiating stem cells into osteoprogenitor cells before transplantation. The method involves culturing stem cells with osteoinductive factors (BMP-2, BMP-7, or BMP-13) and osteogenic supplements (ascorbic acid and dexamethasone) ex vivo to pre-commit them to the osteogenic lineage, ensuring they will contribute to bone tissue formation after transplantation

Inventive Principle:

Principle #10Preliminary action

2Quantity of substance

If the quantity of stem cells is increased to compensate for low differentiation efficiency, then more bone tissue formation may occur, but the available stem cells from bone marrow are frequently unsatisfactory and may be further reduced due to glucocorticoid use, alcohol abuse, or genetic causes

Engineering Contradiction:

Improvenumber of osteogenic cellsVSAvoidstem cell yield from bone marrow

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

The patent applies segmentation by dividing the differentiation process into distinct phases: initial osteoinduction with BMP factors, followed by osteogenic commitment with ascorbic acid and dexamethasone. This segmented approach allows efficient generation of osteoprogenitor cells from limited starting material, achieving high yields of committed osteogenic cells even when bone marrow stem cell availability is reduced

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies parameter changes by systematically varying culture conditions including BMP concentration (5-50 ng/ml), ascorbic acid concentration (50-200 µg/ml), and dexamethasone concentration (0.1-1 µM) to optimize the differentiation efficiency and yield of osteoprogenitor cells from limited stem cell sources

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If existing methods are used to expand and differentiate stem cells, then some osteoblastic phenotype cells can be obtained, but the expansion potential is not sufficiently augmented and additional advantageous properties are not achieved

Engineering Contradiction:

Improvequantity of osteoprogenitor cellsVSAvoidcell properties for transplantation

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent applies composite materials by combining multiple osteoinductive factors (BMP-2, BMP-7, or BMP-13) with osteogenic supplements (ascorbic acid and dexamethasone) in a synergistic culture medium. This composite approach produces osteoprogenitor cells with enhanced properties including improved survival rates, higher differentiation efficiency, and reduced immunogenicity compared to single-factor approaches

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent applies feedback by monitoring differentiation markers (alkaline phosphatase activity, osteocalcin expression, mineralization) during culture and adjusting BMP and osteogenic supplement concentrations accordingly to optimize cell yield and quality for transplantation

Inventive Principle:

Principle #23Feedback

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 method significantly increases the yield of osteogenic cells, reduces tissue sampling requirements, and shortens the time to transplantation, while minimizing tissue rejection risks due to lower HLA-DR expression, making it suitable for allogeneic applications.

Implementation Method 1

culturing said BMSC or MSC in a medium including human plasma or serum, fibroblast growth factor (FGF) and transforming growth factor beta (TGFB)

Methodology Applied

Scientific EffectGrowth factor signaling:

Implementation Method 2

osteogenic differentiation of bone marrow stem cells and mesenchymal stem cells using a combination of growth factors

Methodology Applied

Scientific EffectOsteogenic differentiation:

Data Source

PatentEP2229433B1Osteogenic differentiation of bone marrow stem cells and mesenchymal stem cells using a combination of growth factors

Publication Date: 2017.09.20 BONE THRAPEUTICS SA

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AI summary

The invention relates to methods for osteogenic differentiation of human bone marrow stem cells (BMSC) or mesenchymal stem cells (MSC), in particular using human plasma or serum and FGF and TGFB growth factors. The invention also provides the so-obtained cells and cell populations, as well as further products comprising such and uses thereof in bone therapy.