Statin-Loaded Stem Cells for Ischemic Heart Disease Therapy

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Solution Overview

Problem

Current treatments for ischemic heart diseases, such as myocardial infarction, require local administration of statin-included nanoparticles or stem cells, which is cumbersome, and intravenous administration often necessitates higher doses with potential side effects, while the limited availability of stem cells hinders therapeutic effectiveness.

Innovation Solution

A statin-included nanoparticle preparation is developed, where statin is encapsulated in bioabsorbable nanoparticles with a diameter less than 1000 nm, enhancing the migratory and proliferative capabilities of stem cells, allowing them to efficiently deliver statin to ischemic areas, even when the bloodstream is inhibited, thereby promoting neovascularization and cardiac muscle regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If local administration of statin-included nanoparticles is used, then therapeutic effectiveness is improved, but administration complexity increases

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidadministration complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines stem cells with statin-included nanoparticles to create a composite therapeutic preparation. The stem cells serve as living carriers that can be administered systemically (intravenously) while delivering statin to ischemic areas through their migratory and proliferative capabilities, merging the benefits of local delivery with the ease of systemic administration.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

Stem cells act as intermediary carriers between the statin-included nanoparticles and the ischemic tissue. The stem cells receive the nanoparticles in circulation and transport them to the target area, serving as a biological mediator that overcomes the limitation of direct local administration while maintaining therapeutic effectiveness.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If intravenous administration of statin-included nanoparticles is used, then ease of administration is improved, but required dosage increases and side effects occur

Engineering Contradiction:
Improveease of administrationVSAvoidrequired dosage
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent uses stem cells as biological carriers that replicate and proliferate at the ischemic site, creating a self-amplifying delivery system. Each stem cell carries statin-included nanoparticles and divides to produce more stem cells, effectively copying the delivery function multiple times to achieve high local concentration without requiring high systemic dosage.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The stem cells exhibit migratory capability that directs them to ischemic areas with specific properties (low oxygen, high stress), creating local concentration of statin-included nanoparticles precisely where needed. This local quality accumulation allows reduced systemic dosage while maintaining high effective concentration at the target site.

Inventive Principle:
Principle #3Local quality

3Reliability

If stem cells are administered to treat ischemic heart diseases, then therapeutic effectiveness is improved, but availability of stem cells is limited

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidavailability of stem cells
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent enhances stem cells with statin-included nanoparticles to create multi-functional cells that simultaneously perform: (1) migration to ischemic areas, (2) proliferation to increase numbers, (3) differentiation into cardiac cells, and (4) release of statin. This multi-functionality allows a smaller initial stem cell population to achieve therapeutic effects through amplification and functional integration.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The stem cells are pre-loaded with statin-included nanoparticles before administration. This preliminary action ensures that when the stem cells arrive at the ischemic site and proliferate, they continuously release statin from their internal reservoir, extending the therapeutic effect without requiring additional stem cell administration.

Inventive Principle:
Principle #10Preliminary action

4Reliability

If bloodstream is inhibited in ischemic heart disease, then disease severity is improved, but transport of statin to diseased part is reduced

Engineering Contradiction:
Improvedisease severityVSAvoidtransport speed
Core Design Contradiction:
ReliabilityVSSpeed

Solution Approach 1:

The patent replaces the mechanical bloodstream transport system with a biological transport system. Instead of relying on blood flow to deliver statin to ischemic areas (which is inhibited in the disease), the stem cells use their intrinsic migratory capabilities and phagocytic activity to actively transport and deliver statin-included nanoparticles to the target tissue through cellular mechanisms.

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

Solution Approach 2:

Stem cells serve as intermediary transport vehicles that bypass the inhibited bloodstream. The stem cells circulate in the blood (which is still functional for circulation) and then actively migrate through tissue barriers and accumulate at ischemic sites, acting as a mediator that overcomes the bloodstream inhibition limitation.

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

This approach enables effective treatment of ischemic heart diseases with reduced side effects and lower stem cell doses, as statin-loaded stem cells accumulate, proliferate, and differentiate at ischemic sites, enhancing neovascularization and cardiac muscle regeneration.

Implementation Method 1

the treated stem cells take up statin-included nanoparticles through phagocytosis

Methodology Applied
Scientific EffectPhagocytosis:

Implementation Method 2

the stem cells, which have taken up the statin-included nanoparticles, are enhanced in the migratory capacity

Methodology Applied
Scientific EffectCell migration:

Implementation Method 3

the stem cells accumulate and proliferate at an ischemic part, and release neovascularization factors to promote neovascularization of the ischemic part. Moreover, the accumulated and proliferating stem cells differentiate into cardiac muscle

Methodology Applied
Scientific EffectCell differentiation:

Data Source

PatentEP3777890A1Stem cells containing statin-encapsulated nanoparticles
Publication Date: 2021.02.17 FOUND FOR BIOMEDICAL RES & INNOVATION
  • EP3777890A1 patent drawingFigure 1
  • EP3777890A1 patent drawingFigure 2
  • EP3777890A1 patent drawingFigure 3(a)~3(b)

AI summary

The present invention is directed to a stem cell with an enhanced function, the stem cell comprising a statin-included nanoparticle preparation for enhancing a function of the stem cell, the statin-included nanoparticle preparation comprising: a statin-included nanoparticle obtained by including statin in a nanoparticle, containing a bioabsorbable polymer, wherein the nanoparticle has a number average particle diameter of less than 1000 nm, and wherein the function of the stem cell which is to be enhanced is at least one of a migratory capacity, a proliferation capacity, and the production of a neovascularization factor.