Muse Cell Preparation for Diabetic Skin Ulcer Regeneration

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Solution Overview

Problem

Current treatments for skin ulcers, particularly those caused by diabetes, are inadequate in achieving complete recovery due to limitations in existing pluripotent stem cell therapies, such as variability in therapeutic effects and tumorigenic risks associated with induced pluripotent stem cells.

Innovation Solution

A cell preparation comprising SSEA-3-positive pluripotent stem cells, known as Muse cells, which are isolated from mesenchymal tissue and characterized by specific surface markers, are administered to promote skin tissue regeneration by differentiating into cells that repair and rebuild skin tissue at the ulcer site.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If induced pluripotent stem cells are used for skin ulcer treatment, then cell proliferation and differentiation capacity is improved, but tumorigenic risk increases

Engineering Contradiction:

Improvecell proliferation and differentiation capacityVSAvoidtumorigenic risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and isolates a specific subpopulation of pluripotent stem cells (SSEA-3-positive cells) from mesenchymal stem cells. This extraction approach separates the beneficial therapeutic cells from the harmful tumorigenic components, achieving both high proliferation/differentiation capacity and safety by selecting only the non-tumorigenic pluripotent subset through surface marker identification

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention applies local quality by characterizing and selecting cells with specific surface marker expressions (SSEA-3 positive, CD105 positive, CD117 negative, CD146 negative). This creates a locally optimized cell population with precise functional properties - maintaining pluripotency and differentiation capacity while eliminating tumorigenicity through specific phenotypic selection

Inventive Principle:

Principle #3Local quality

2Reliability

If mesenchymal stem cells are used for skin ulcer treatment, then safety is improved, but therapeutic effect variability increases

Engineering Contradiction:

ImprovesafetyVSAvoidtherapeutic effect variability

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The invention changes the selection parameters for stem cell therapy by using specific surface marker expressions (SSEA-3, CD105, CD117, CD146) as selection criteria. This parameter-based selection methodology transforms the heterogeneous mesenchymal stem cell population into a standardized, homogeneous pluripotent cell population with consistent therapeutic effects and reduced variability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention achieves homogeneity by isolating a specific subpopulation of cells with identical surface marker profiles (SSEA-3 positive, CD105 positive, CD117 negative, CD146 negative). This creates a uniform cell population with consistent pluripotent characteristics and predictable therapeutic outcomes, eliminating the variability inherent in traditional mesenchymal stem cell preparations

Inventive Principle:

Principle #33Homogeneity

3Productivity

If adipose-derived stromal cells are used for ischemic injury treatment, then vascular regeneration is improved, but complete tissue recovery is not achieved

Engineering Contradiction:

Improvevascular regeneration capacityVSAvoidcomplete tissue recovery

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The invention applies universality by using SSEA-3-positive pluripotent stem cells that can differentiate into multiple lineages including vascular endothelial cells, adipocytes, nerve cells, and skin cells. This multi-functional cell population can simultaneously perform vascular regeneration, tissue reconstruction, and nerve repair, achieving complete tissue recovery rather than just vascular regeneration

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 use of Muse cells effectively inhibits the progression of skin ulcers and facilitates complete healing by differentiating into skin tissue components, demonstrating superior wound healing in diabetic mouse models compared to mesenchymal stem cells.

Implementation Method 1

pluripotent stem cells positive for SSEA-3 isolated from biological mesenchymal tissue or cultured mesenchymal cells... differentiating into cells that repair and rebuild skin tissue at the ulcer site

Methodology Applied

Scientific EffectCell differentiation:

Data Source

PatentUS11000552B2Pluripotent stem cell for treating diabetic skin ulcer

Publication Date: 2021.05.11 THE UNIV OF TOKYO

AI summary

The purpose of the present invention is to provide a novel medicinal use in regeneration medicine, said medicinal use comprising using pluripotent stem cells (Muse cells). Provided is a cell preparation for treating skin ulcer, said cell preparation comprising SSEA-3 positive pluripotent stem cells isolated from a mesenchymal tissue of a living organism or cultured mesenchymal cells. The cell preparation according to the present invention is based on such mechanism of skin tissue regeneration that, when the Muse cells are administered to a skin ulcer site of a subject suffering from the aforesaid disease, the Muse cells differentiate into skin-constituting cells.