FENC Stem Cell Isolation via FACsorting Antibody Selection

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Solution Overview

Problem

Current methods for isolating stem cells from human tissues face challenges in achieving unlimited proliferation and differentiation capabilities similar to embryonic stem cells, as adult stem cells lack totipotency and handling embryonic cells for therapeutic and research purposes encounters ethical, legal, and technical difficulties.

Innovation Solution

A method for isolating a non-haematopoietic, mesenchymal stem subpopulation, FENC (Follicle-derived Embryonic Neural Crest stem cells), using FACsorting selection with specific antibodies, allowing for the expansion and differentiation of cells into all three germinal layers, enabling the creation of a totipotent/multipotent cell population that can be stored and used for therapeutic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If adult stem cells are isolated from human tissues, then the cells can be collected for therapeutic use, but they lack unlimited proliferation ability and totipotency

Engineering Contradiction:
Improvetherapeutic utilityVSAvoidproliferation and differentiation capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention segments the stem cell isolation process into distinct steps: initial collection of follicular tissue, enzymatic digestion to release individual cells, and subsequent FACsorting based on specific surface markers. This segmentation allows for progressive purification and selection of cells with desired embryonic-like characteristics while maintaining their therapeutic potential

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the selection parameters from conventional adult stem cell markers to embryonic stem cell surface markers (SSEA-4, TRA-1-60, TRA-1-81). This parameter change enables the isolation of cells with embryonic-like proliferation and differentiation capabilities from adult human tissue, resolving the contradiction between therapeutic utility and cellular versatility

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If embryonic stem cells are used for therapeutic and research purposes, then unlimited proliferation and totipotency are achieved, but technical, ethical and legal difficulties arise

Engineering Contradiction:
Improveproliferation and differentiation capabilityVSAvoidethical and legal complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention uses FACsorting with specific surface markers as an intermediary technique to obtain embryonic-like stem cells from adult human tissue without requiring actual embryonic material. This intermediary approach provides a legal and ethical alternative that mimics embryonic stem cell properties while avoiding the associated ethical and legal complexities

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a copy of embryonic stem cell properties (surface markers, proliferation capacity, differentiation potential) in cells derived from adult human tissue. By copying the essential characteristics of embryonic stem cells without using embryos, the invention achieves therapeutic versatility while avoiding ethical and legal issues

Inventive Principle:
Principle #26Copying

3Quantity of substance

If conventional isolation methods are used, then stem cells can be collected, but the population is heterogeneous and lacks embryonic-like characteristics

Engineering Contradiction:
Improvecell yieldVSAvoidcell population homogeneity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The invention replaces conventional mechanical or non-specific selection methods with FACsorting, a flow cytometry-based technique that uses fluorescently labeled antibodies to specifically identify and isolate cells expressing embryonic stem cell surface markers. This substitution enables precise selection of homogeneous cell populations with desired characteristics while maintaining adequate cell yield

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 method provides a low-invasive, high-clonogenic stem cell isolation with minimal tissue sacrifice, enabling the use of embryonic-like stem cells for autologous therapeutic applications, including tissue engineering and cell therapy, with cells capable of differentiating into various tissue types without causing cancer, as demonstrated by successful transplantation and histological observations.

Implementation Method 1

FACsorting selection, after suitable staining with specific antibodies

Methodology Applied
Scientific EffectAntigen-antibody binding: Adsorption

Implementation Method 2

selection by cytofluorimetry of embryonic stem cells, through antigens detection such as SSEA-4, TRA 1-60, TRA 1-81

Methodology Applied
Scientific EffectFlow cytometry:

Data Source

PatentUS8187879B2Collection and selection methods to isolate a stem cell population from human adult periodontal follicular tissues
Publication Date: 2012.05.29 POLO TECH PIEMONTESE SRL

AI summary

Methods for the isolation, expansion and storage of a population of stem cells belonging to human dental follicles, called FENC (Follicle-derived Embryonic Neural Crest stem cells,) including: a) Collection of the follicular sack in sterile conditions, digestion and primary culture growth and expansion; b) Optional amplification; c) FACsorting.