CD264 Marker for Early MSC Aging Identification

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Solution Overview

Problem

Current methods fail to effectively identify and isolate early aging mesenchymal stem cells (MSCs) in heterogeneous cultures, which limits the regenerative potential and therapeutic efficacy of MSC therapies.

Innovation Solution

The use of CD264 as a novel cell-surface marker to identify and sort early aging MSCs, allowing for the enrichment of populations with higher proliferation and differentiation potential by removing senescent cells, thereby improving the regenerative properties of MSCs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods (NG2, CD146 markers) are used to identify MSCs, then MSC population homogenization is achieved, but early aging MSCs cannot be specifically identified and removed

Engineering Contradiction:
Improveidentification precision of early aging MSCsVSAvoidability to detect early aging stage
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent changes the detection parameter from conventional surface markers (NG2, CD146) to a new marker (CD264) that specifically detects early aging MSCs. This parameter change enables precise identification of the early aging stage that was previously undetectable, resolving the contradiction between population homogenization and early aging detection.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If heterogeneous MSC cultures are used, then cell diversity is maintained, but regenerative potential and therapeutic efficacy are reduced due to senescent cells

Engineering Contradiction:
Improveregenerative potentialVSAvoidproportion of senescent cells
Core Design Contradiction:
Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent extracts and removes early aging MSCs from heterogeneous cultures using the CD264 marker for specific identification. By taking out the senescent cells at the early aging stage, the regenerative potential of the remaining culture is enhanced while maintaining cell diversity, resolving the contradiction between adaptability and senescent cell quantity.

Inventive Principle:
Principle #2Taking out (Extraction)

3Reliability

If senescent cells are removed from MSC cultures, then therapeutic efficacy is improved, but the ability to identify early aging cells is limited by current marker technology

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoiddetection of early aging MSCs
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent introduces a new detection parameter (CD264 surface marker) that enables reliable identification of early aging MSCs. This parameter change makes detection feasible and allows for effective removal of senescent cells, thereby improving therapeutic efficacy while overcoming the detection difficulty.

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 identification and removal of CD264+ cells lead to a culture enriched with young, non-senescent MSCs, enhancing the regenerative and proliferative potential, and colony-forming efficiency, thus improving the efficacy of stem cell treatments.

Implementation Method 1

MSC population homogenization is achieved by detecting surface antigens using fluorescently labeled antibodies and fluorescence-activated cell sorting (FACS)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

Flow cytometry is used in the sorting process. Cells with high surface expression of the antigen and cells with low surface expression of the antigen can be differentiated and separated by the flow cytometer

Methodology Applied
Scientific EffectFlow cytometry:

Implementation Method 3

If a fluorescent proliferation dye is chosen, FACS can be employed to separate subpopulations that either divide rapidly or slowly

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3129469B1Cell-surface marker of early MSC aging
Publication Date: 2022.07.27 THE ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND
  • EP3129469B1 patent drawingFigure 1
  • EP3129469B1 patent drawingFigure 2
  • EP3129469B1 patent drawingFigure 3A~3E

AI summary

This invention relates to a cell-surface marker for identifying MSC that are aging. This invention also relates to a method of screening MSCs of low proliferation potential and trilineage potential by removing CD264+ MSCs from the population.