3D Cell Structure Thickness Maintenance via Stromal Cell Selection

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Solution Overview

Problem

Three-dimensional cell structures produced using mouse-derived cells tend to decrease in thickness over time, which is not observed with human-derived cells, posing a challenge for maintaining structural integrity in applications like cancer models and tissue models.

Innovation Solution

A method involving a mixture of endothelial cells, mouse-derived stromal cells excluding endothelial cells, a cationic substance, an extracellular matrix component, and a polyelectrolyte is used to produce three-dimensional cell structures, with a specific ratio of endothelial cells to stromal cells and specific concentrations of these components to suppress the decrease in thickness over time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If mouse-derived cells are used to produce three-dimensional cell structures, then the production process is feasible and cost-effective, but the thickness of the cell structures decreases over time

Engineering Contradiction:
Improveproduction feasibilityVSAvoidthickness maintenance
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent changes the compositional parameters of the cell population by specifically excluding mouse-derived endothelial cells while retaining other mouse-derived stromal cells. This parameter modification prevents the thickness decrease phenomenon while maintaining the use of mouse-derived cells for production

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the potential harm of using mouse-derived cells (which causes thickness decrease) into a benefit by identifying and removing only the specific problematic cell type (mouse-derived endothelial cells), thereby retaining the advantages of mouse-derived cell production while eliminating the disadvantage

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

2Stability of the object's composition

If a specific cell population composition is used to maintain thickness, then structural stability is improved, but the cell population selection becomes more complex

Engineering Contradiction:
Improvethickness maintenanceVSAvoidcell population selection
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent simplifies the complexity by establishing a clear parameter criterion: excluding only mouse-derived endothelial cells while allowing all other mouse-derived stromal cells. This single parameter change provides a straightforward selection rule that maintains stability without complex population management

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 method effectively maintains the thickness of three-dimensional cell structures produced using mouse-derived cells, ensuring structural stability and integrity comparable to those produced with human-derived cells, with the maximum width of slices on the fifth day being at least 50% of the initial width.

Implementation Method 1

a mixture in which cells are suspended in a solution comprising at least a cationic buffer solution, an extracellular matrix component, and a polyelectrolyte

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

obtaining a mixture of a cell population, a cationic substance, an extracellular matrix component, and a polyelectrolyte

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS20230193211A1Method for producing three-dimensional cell structure, and three-dimensional cell structure
Publication Date: 2023.06.22 TOPPAN INC
  • US20230193211A1 patent drawing
  • US20230193211A1 patent drawing
  • US20230193211A1 patent drawing

AI summary

A method for producing a three-dimensional cell structure includes preparing a mixture of a cationic substance, an extracellular matrix component, a polyelectrolyte, and a cell population including endothelial cells and mouse-derived stromal cells, which exclude mouse-derived endothelial cells, collecting a cell aggregate from the mixture, and culturing a collected cell aggregate to obtain a three-dimensional cell structure.