Lgr5+ Somatic Stem Cell Isolation via Density Gradient

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Solution Overview

Problem

There is a need for adult somatic stem cells that can be easily isolated and maintained, as multipotent adult progenitor cells from bone marrow are difficult to obtain, culture, and expand due to their pluripotency and ethical considerations surrounding embryonic stem cells.

Innovation Solution

Isolation and preparation of Lgr5+ SB cells, which are adult stem cells less than 6.0 μm in size, positive for Lgr5, and capable of differentiating into ectoderm, endoderm, and mesoderm cells, using a method involving EDTA or heparin treatment of tissue samples to separate and enrich these cells, allowing for their use in treating various degenerative disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multipotent adult progenitor cells from bone marrow are used, then differentiation capability into multiple lineages is achieved, but isolation and culture difficulty increases

Engineering Contradiction:
Improvedifferentiation capabilityVSAvoidisolation and culture difficulty
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent extracts and isolates a specific subpopulation of adult stem cells (2-6 μm in size, Lgr5+) from bone marrow that possesses pluripotent differentiation capabilities. This extraction approach identifies and separates the most versatile cells while removing less useful components, thereby achieving both high differentiation potential and easier isolation through defined physical and molecular criteria

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies parameter changes by defining specific cell characteristics (size: 2-6 μm, Lgr5 positivity) to identify and isolate the desired stem cell population. These parameter specifications enable systematic separation and culture of cells with optimal differentiation potential while simplifying the isolation process through measurable criteria

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If embryonic stem cells are used for treatment, then pluripotency and differentiation potential are maximized, but ethical considerations and regulatory hurdles increase

Engineering Contradiction:
ImprovepluripotencyVSAvoidethical considerations
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses Lgr5+ adult stem cells as an intermediary solution that bridges the gap between embryonic and conventional adult stem cells. These cells provide pluripotent differentiation capabilities similar to embryonic stem cells but are derived from adult bone marrow, thereby avoiding the ethical issues associated with embryo destruction while maintaining therapeutic potential

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs adult stem cells that can be harvested from the patient's own bone marrow, creating a self-contained, ethically acceptable alternative to embryonic stem cells. This approach eliminates the need for controversial embryonic sources while providing sufficient differentiation potential for regenerative therapy

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

The Lgr5+ SB cells can be easily prepared, maintained, and expanded in vitro, inducing differentiation without malignant growth, making them a viable alternative for regenerative therapies and tissue repair, with no evidence of contamination or immune rejection, and can form all somatic and reproductive cells.

Implementation Method 1

incubating the sample with EDTA or heparin in a container until the sample is separated into an upper layer and a lower layer

Methodology Applied
Scientific EffectDensity gradient separation: Density Gradient

Data Source

PatentUS11492592B2Lgr5+ somatic stem cells
Publication Date: 2022.11.08 STEMBIOS TECHNOLOGIES INC

AI summary

A method for treating a condition, comprising administering to a subject in need thereof a composition that contains somatic stem cells that are 2 to less than 6 micrometers in size and Lgr5+, wherein the condition is selected from the group consisting of neurodegenerative disorder, muscle-degenerative disease, cancer, metabolic disorder, autoimmune disorder, inflammatory disorder, heart disorder, circulatory disorder, a condition associated with aging, and damaged tissue.