TUDCA Treatment for Stem Cell Mobilization and Senescence Inhibition

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Solution Overview

Problem

Current stem cell therapies face challenges such as limited supply, senescence of stem cells during in vitro expansion, and lower survival rates in ischemic tissues, along with difficulties in accurate migration and differentiation of stem cells, which hinder their effectiveness in treating ischemic diseases.

Innovation Solution

Treatment of stem cells with tauroursodeoxycholic acid (TUDCA) or its pharmaceutically acceptable salts to promote migration, induce differentiation, and inhibit senescence, thereby enhancing the functionality and mobilization of angiogenic stem cells from bone marrow to ischemic tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cytokines (GCSF, GM-CSF, SDF-1, VEGF) are used to mobilize angiogenic stem cells from bone marrow, then stem cell mobilization is improved, but inflammation is caused and application challenges arise

Engineering Contradiction:

Improvestem cell mobilization efficiencyVSAvoidinflammation

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses TUDCA as an intermediary substance that mediates stem cell mobilization without triggering inflammation. TUDCA acts as a chemical chaperone that protects endothelial cells from oxidative stress and facilitates stem cell release from bone marrow through a non-inflammatory pathway, thereby resolving the contradiction between effective mobilization and inflammation prevention

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the mobilization approach by using TUDCA, a bile acid derivative, instead of traditional cytokines. This parameter change shifts the mechanism from receptor-mediated inflammatory signaling to oxidative stress protection and chemical chaperone activity, achieving mobilization without inflammation

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If stem cells are expanded in vitro to obtain sufficient quantity, then cell supply is improved, but senescence occurs and function degrades

Engineering Contradiction:

Improvestem cell quantityVSAvoidstem cell function

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent applies TUDCA treatment before and during in vitro expansion of stem cells to prevent senescence proactively. By pre-treating stem cells with TUDCA, which acts as a chemical chaperone protecting against oxidative stress and ER stress, the cells maintain their functional properties throughout the expansion process, thereby resolving the contradiction between quantity increase and function preservation

Inventive Principle:

Principle #10Preliminary action

3Productivity

If stem cells are transplanted to ischemic tissue, then tissue repair is improved, but survival rate is low due to degraded function and senescence

Engineering Contradiction:

Improvetissue repair efficiencyVSAvoidstem cell survival rate

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies TUDCA as a protective agent before transplantation to cushion stem cells against the harsh ischemic environment. TUDCA pre-treatment enhances cell survival by protecting against oxidative stress, ER stress, and apoptosis, thereby resolving the contradiction between tissue repair efficiency and survival rate

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

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

TUDCA treatment significantly increases the mobilization and integration of angiogenic stem cells into vascular endothelial cells, enhances their differentiation potential, and inhibits senescence, leading to improved vascular repair and therapeutic outcomes in ischemic diseases, including increased blood flow and capillary formation.

Implementation Method 1

TUDCA acts as a chemical chaperone to maintain protein stability

Methodology Applied

Scientific EffectChemical chaperone effect:

Implementation Method 2

TUDCA suppresses endoplasmic reticulum stress (ER-stress), thereby protecting cells in damaged tissue

Methodology Applied

Scientific EffectEndoplasmic reticulum stress suppression:

Implementation Method 3

TUDCA controls the apoptosis signal transmission system which is proceeded in the mitochondria, and prevents apoptosis with its role by promoting the activation of anti-apoptotic signal factors

Methodology Applied

Scientific EffectApoptosis signal inhibition:

Data Source

PatentUS9896662B2Process for enhancing stem cell bioactivity using tauroursodeoxycholic acid

Publication Date: 2018.02.20 PUSAN NAT UNIV IND UNIV COOPERATION FOUND

AI summary

The present invention relates to a process for enhancing stem cell bioactivity using tauroursodeoxycholic acid (TUDCA) or a pharmaceutical acceptable salt thereof.