Skeletal Stem Cell Isolation Using Specific Surface Markers

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Solution Overview

Problem

There is a need for effective cell markers to identify and isolate skeletal stem cells (SSCs) and suture stem cells (SuSCs) for regenerative medicine applications, as their in vivo identity remains largely elusive.

Innovation Solution

The method involves obtaining a start cell population and identifying specific markers expressed by the cells, such as those listed in Tables 1 and 2, to selectively isolate and enrich SSCs and SuSCs. This can be achieved using agents that specifically bind to these markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cell markers are identified and isolation methods are developed, then skeletal stem cells can be effectively isolated and enriched for regenerative medicine applications, but the complexity of identification and isolation processes increases

Engineering Contradiction:
Improveidentification and isolation of skeletal stem cellsVSAvoidcomplexity of identification and isolation methods
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the complex isolation process into multiple sequential steps: initial cell population obtaining, marker identification (using multiple markers from Tables 1 and 2), selective isolation, and enrichment. This segmentation allows each step to be optimized independently and makes the overall complex process more manageable and reproducible for regenerative medicine applications.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs specific cell markers (such as Bmpr1a, Bmpr2, Fgfr2, Lrig3, Itgbl1, and others listed in Tables 1 and 2) as intermediary elements that mediate between the complex cellular environment and the isolation process. These markers serve as identifiable targets that enable selective binding and isolation of skeletal stem cells from heterogeneous cell populations, thereby reducing the effective complexity of the isolation procedure.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If multiple cell markers are used to improve isolation accuracy, then the purity of skeletal stem cell population increases, but the time required for identification and isolation procedures increases

Engineering Contradiction:
Improveaccuracy of skeletal stem cell identificationVSAvoidtime for identification and isolation procedures
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies partial action by providing a curated list of essential markers (Tables 1 and 2) that are sufficient for effective skeletal stem cell isolation. Rather than requiring all possible markers, the patent identifies a manageable set of markers (such as Bmpr1a, Bmpr2, Fgfr2, Lrig3, Itgbl1, Apoe, Gpc3, Lpl, Sulf2, Cdon, Tgfbr2, Tgfbr3, Lrrc15, Mif, Axl, Itgav, Fgfr1, Jag1, Acvr1, Acvr2a, Acvr2b, Bmpr2, Erg, Six2, Pthlh, Twist1, Alpl, Msx1, Efnb1, Zic1, Spry1, Abcc9, Erf, Bmp2, Bmp3, Bmp4, Bmp5, Bmp6, Bmp7, Bmp8a, Bambi, Bmper, and Col3a1) that achieves the required isolation accuracy, thereby reducing the time needed for multi-parameter analysis.

Inventive Principle:
Principle #16Partial or excessive action

3Quantity of substance

If specific binding agents are used to isolate cells expressing markers, then the enrichment of skeletal stem cells is improved, but the cost and complexity of reagents increases

Engineering Contradiction:
Improveenrichment of skeletal stem cell populationVSAvoidcomplexity and cost of isolation reagents
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent employs disposable, commercially available antibodies and binding agents targeting the identified markers (such as Bmpr1a, Bmpr2, Fgfr2, Lrig3, Itgbl1, etc.) for cell isolation. These reagents are designed for single-use applications, eliminating the need for expensive, complex, and maintenance-intensive research-grade reagents. The markers and their corresponding binding agents can be obtained from standard commercial sources, significantly reducing the cost and complexity of the enrichment process while maintaining high skeletal stem cell population purity.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 approach allows for the successful identification, isolation, and enrichment of SSCs and SuSCs, which can be used for stem cell-based therapies, including bone regeneration and cartilage or bone generation in subjects.

Implementation Method 1

The cell or cells can be identified, isolated, or enriched using a first agent (such as a first protein, a first polypeptide, a first nucleic acid, or a first composition) that specifically binds to the first marker.

Methodology Applied
Scientific EffectSpecific binding:

Data Source

PatentUS20250137072A1Markers for skeletal stem cell and uses thereof
Publication Date: 2025.05.01 ADA FORSYTH INSTITUTE INC
  • US20250137072A1 patent drawing
  • US20250137072A1 patent drawing
  • US20250137072A1 patent drawing

AI summary

This application relates to stem cell biology and regenerative medicine. Disclosed herein are methods for isolation of skeletal stem cells, related methods, related compositions, related products, and related uses.