In Vitro Cell Selection for Enhanced Migration and Tissue Regeneration

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Solution Overview

Problem

Current cell-based therapies for degenerative diseases face challenges such as inefficient cell migration and survival in the central nervous system, immune reactions, and failure to regenerate tissue effectively, highlighting the need for a method to select subpopulations with enhanced migration potential and safety for therapeutic use.

Innovation Solution

A method involving the in vitro selection of therapeutic cell subpopulations from eukaryotic cells using a reservoir system with specific pore sizes and cell culture media, where cells with elevated migration potential are identified and further selected using agents binding to markers like podoplanin, CD146, and CD44, enhancing their migratory capacity and tropism.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If stem cells are used for cell-based therapy, then tissue regeneration potential is improved, but migration efficiency and targeting capability to the target tissue deteriorate

Engineering Contradiction:
Improvetissue regeneration potentialVSAvoidmigration efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent extracts and isolates a specific subpopulation of stem cells with enhanced migration capabilities from the original heterogeneous cell population. By using in vitro selection methods, the patent separates the highly migrative cells from less efficient cells, thereby improving migration efficiency while maintaining the tissue regeneration potential of the selected subpopulation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent enhances the local quality of specific cells within the population by selecting for cells that express particular surface markers or exhibit specific migratory behaviors. This creates a subpopulation with localized enhanced properties (migration efficiency) while preserving the overall therapeutic potential of the stem cell population.

Inventive Principle:
Principle #3Local quality

2Reliability

If stem cells are transplanted into the target tissue, then therapeutic effect is improved, but immune reactions and cell survival issues worsen

Engineering Contradiction:
Improvetherapeutic effectVSAvoidimmune reactions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent performs preliminary selection and conditioning of stem cells in vitro before transplantation. By pre-selecting cells with enhanced migratory and survival capabilities, and potentially pre-conditioning them in controlled environments, the patent prepares the cells to better withstand immune reactions and survive in the target tissue, thereby improving therapeutic effect while mitigating immune-related harmful factors.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If cell population is increased for better tissue coverage, then regeneration effectiveness is improved, but cell migration control and targeting worsen

Engineering Contradiction:
Improveregeneration effectivenessVSAvoidcell targeting precision
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

Rather than simply increasing the total cell population, the patent extracts and enriches a specific subpopulation of cells with enhanced migratory and targeting capabilities. This approach allows for effective tissue coverage through improved cell distribution and migration, while maintaining precise targeting control because the selected cells inherently possess better navigation and homing abilities to the target tissue.

Inventive Principle:
Principle #2Taking out (Extraction)

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 selected subpopulations demonstrate improved migration and targeting capabilities to specific tissues, leading to more effective and faster regeneration of degenerated tissue, as shown by increased migration speed, differentiation potential, and biodistribution in animal models of neurodegenerative diseases and tumors.

Implementation Method 1

a starting reservoir, which is connected via at least one selection means having at least one opening to at least one selection reservoir, wherein the at least one opening of the at least one selection means has a diameter of 3 μm to 500 μm

Methodology Applied
Scientific EffectPhysical filtration: Filter (physical)

Implementation Method 2

wherein the at least one opening of the at least one selection means has a diameter of 3 μm to 500 μm; culturing of the original cell population for a period of 15 min to 48 hours, within which period a cell subpopulation migrates through the at least one opening

Methodology Applied
Scientific EffectSize-based separation: Centrifugal Separation

Implementation Method 3

e) selection of a highly migrative cell subpopulation from the cell subpopulation obtained in step d) using at least one agent specifically binding to a cell marker, the cell marker being selected from podoplanin, Sca-1, CD146 and CD44

Methodology Applied
Scientific EffectAntigen-antibody binding: Adsorption

Data Source

PatentEP3262154B1Cell selection method and cells obtained therefrom
Publication Date: 2020.11.11 EBERHARD KARLS UNIV TUBINGEN MEDIZINISCHE FAKULTAT
  • EP3262154B1 patent drawingFigure 1A~1B
  • EP3262154B1 patent drawingFigure 1C~1D
  • EP3262154B1 patent drawingFigure 2

AI summary

The present invention relates to a method for the in vitro selection of at least one therapeutic cell subpopulation from an original cell population of eukaryotic cells, as well as to the therapeutic cell subpopulation selected by the method, which can be used for the treatment of diseases of tissues or organs. The selected cells are highly migrative and the method according to the invention provides for the selection of these highly migrative subpopulations from a sample comprising a mixture of cells.