Glia-like Cells from Late-Passage hMSCs for Stroke Therapy

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Solution Overview

Problem

Current treatments for stroke using early-passage human mesenchymal stem cells are limited by low paracrine activity and difficulty in obtaining sufficient cell quantities, while late-passage cells have decreased effectiveness due to lower growth factor secretion, necessitating a more effective approach to enhance nervous system recovery.

Innovation Solution

Induction of late-passage human mesenchymal stem cells into glia-like cells (ghMSCs) to enhance paracrine activity, which secretes high amounts of growth factors and cytokines, thereby improving microenvironmental support and neural function recovery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If early-passage human mesenchymal stem cells are used for stroke treatment, then sufficient cell quantities can be obtained, but paracrine activity and growth factor secretion are limited

Engineering Contradiction:

Improvecell quantityVSAvoidparacrine activity

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the passage parameter of hMSCs from early-passage to late-passage (≥10 passages), and induces differentiation into glia-like cells, thereby transforming the cellular characteristics to achieve both sufficient quantity and enhanced paracrine activity simultaneously

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If late-passage human mesenchymal stem cells are used for stroke treatment, then sufficient cell quantities can be obtained, but effectiveness decreases due to lower growth factor secretion

Engineering Contradiction:

Improvecell quantityVSAvoiddecreased effectiveness

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent changes the differentiation state parameter by inducing late-passage hMSCs to differentiate into glia-like cells, which restores and enhances growth factor secretion capability while maintaining sufficient cell quantity for treatment

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses glia-like cell differentiation as an intermediary transformation process, converting late-passage hMSCs into a cell type with enhanced therapeutic functionality, thereby mediating between the quantity advantage of late-passage cells and the effectiveness requirement

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If embryonic stem cells or induced pluripotent stem cells are used to replace damaged neurons, then nervous system restoration is possible, but unwanted cancer may occur

Engineering Contradiction:

Improvenervous system restorationVSAvoidcancer risk

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses adult stem cells (hMSCs) that are easier to obtain and have lower tumorigenicity compared to embryonic or induced pluripotent stem cells, accepting that they have more limited differentiation capacity but providing a safer alternative with sufficient therapeutic effect through paracrine mechanisms

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent uses hMSCs as an intermediary cell type that provides therapeutic benefit through differentiation into glia-like cells and paracrine factor secretion, rather than directly replacing neurons, thereby achieving nervous system restoration without the cancer risks associated with pluripotent stem cells

Inventive Principle:

Principle #24Intermediary (Mediator)

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 ghMSCs significantly reduces infarct volume by 50% or more and improves neural functions in animal models, primarily through the Akt pathway of IGFBP-4 via IGF-1R, demonstrating a robust therapeutic effect for ischemic stroke.

Implementation Method 1

Late-passage human mesenchymal stem cells induced into glia-like cells (ghMSCs) as an active ingredient for treatment of stroke... ghMSCs secrete high amounts of growth factors and cytokines, thereby improving microenvironmental support and neural function recovery

Methodology Applied

Scientific EffectParacrine secretion:

Implementation Method 2

The use of ghMSCs significantly reduces infarct volume by 50% or more and improves neural functions in animal models, primarily through the Akt pathway of IGFBP-4 via IGF-1R

Methodology Applied

Scientific EffectSignal transduction pathway:

Data Source

PatentUS20220331368A1Pharmaceutical composition comprising glia-like cells induced from late-passage human mesenchymal stem cells as active ingredient for treatment of stroke

Publication Date: 2022.10.20 SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION

AI summary

The present invention relates to a pharmaceutical composition comprising glia-like cells differentiated from human mesenchymal stem cells as an active ingredient for treatment of stroke. Specifically, as a result of injecting the glia-like cells differentiated from human mesenchymal stem cells (ghMSCs) of the present invention to cerebral infarction-induced animal models, the infarct volume remarkably decreased by 50% or more and neural functions were remarkably improved, compared to a control group and a group treated with human mesenchymal stem cells (hMSCs), demonstrating that ischemic stroke (infarction) is treated by the Akt pathway of IGFBP-4 via IGF-1R. Thus, the differentiated glia-like cells of the present invention can be advantageously used as a cell therapy product for stroke.