XPR1 Surface Transporter Biomarker for Cell Aging Assessment

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Solution Overview

Problem

Current methods for assessing cell aging in stem cells, particularly mesenchymal stem cells (MSCs), are complex due to the need for intracellular protein detection, which requires cell permeabilization, and lack early biomarkers for senescence, making it difficult to evaluate the therapeutic potential and quality of cell batches for regenerative medicine.

Innovation Solution

The use of XPR1 as a cell surface nutrient transporter biomarker to assess cell aging by measuring its expression level, either at the RNA or protein level, and comparing it to a reference, allowing for the evaluation of cell aging and the potential impact of compounds on aging processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If intracellular protein detection methods are used to assess cell aging, then measurement precision can be achieved, but device complexity and ease of operation deteriorate due to required cell permeabilization

Engineering Contradiction:
Improvecell aging assessment accuracyVSAvoiddetection method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts the detection target from the intracellular environment to the cell surface by using XPR1, a cell surface nutrient transporter, as the aging biomarker. This eliminates the need for cell permeabilization while maintaining detection accuracy, directly resolving the contradiction between measurement precision and device complexity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses cell surface nutrient transporters (XPR1, GLUT1, GLUT3, GLUT4) as intermediary markers that reflect intracellular aging processes without requiring direct intracellular access. These surface markers serve as mediators between the aging process and the detection system, simplifying the overall detection methodology

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If intracellular protein detection is performed, then reliable cell aging assessment is achieved, but ease of operation worsens due to permeabilization requirements

Engineering Contradiction:
Improvecell aging assessment reliabilityVSAvoiddetection procedure simplicity
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The detection target is extracted from intracellular proteins to cell surface transporters, eliminating the permeabilization step and making the assay easier to perform while maintaining reliability through the use of age-dependent surface marker expression

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The cell surface transporters naturally present the aging information on the cell surface without requiring cellular disruption. The detection system interacts with these self-presented markers, making the operation simpler while preserving assessment reliability

Inventive Principle:
Principle #25Self-service

3Measurement precision

If conventional cell aging assays are used, then comprehensive aging evaluation is achieved, but loss of time increases due to complex procedures

Engineering Contradiction:
Improveaging assessment accuracyVSAvoidassay execution time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

By extracting the detection target to cell surface markers, the assay eliminates time-consuming permeabilization steps and complex sample preparation, reducing total assay time while maintaining accurate aging assessment through the age-specific expression patterns of surface transporters

Inventive Principle:
Principle #2Taking out (Extraction)

4Measurement precision

If early biomarkers for senescence are not available, then comprehensive aging assessment is achieved, but loss of time increases due to inability to detect early stages

Engineering Contradiction:
Improveearly senescence detection capabilityVSAvoidtime to detect aging onset
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention enables preliminary detection of cell aging by monitoring expression changes of cell surface nutrient transporters (particularly XPR1) that occur early in the aging process. This allows early intervention and assessment before full senescence develops, reducing the time needed to detect aging onset while maintaining precision

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3186386B1In vitro assays for assessing cell aging
Publication Date: 2021.05.26 METAFORA BIOSYST
  • EP3186386B1 patent drawingFigure 1A~1B
  • EP3186386B1 patent drawingFigure 1C~1D
  • EP3186386B1 patent drawingFigure 2

AI summary

The present invention relates to an in vitro method for assessing, evaluating, monitoring or predicting cell aging of a cell, wherein said method comprises measuring the expression level of at least one cell surface nutrient transporter on said cell.