Cardiac Stem Cell Spheroid Preparation for Ischemic Heart Disease

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Solution Overview

Problem

Current stem cell therapies for ischemic heart disease face challenges due to high cell death rates of transplanted stem cells at ischemic sites, making existing treatments ineffective for necrotic tissues and unsuitable for clinical applications.

Innovation Solution

A method for preparing cardiac stem cell spheroids by seeding cells at specific densities in a culture vessel with cell adhesion inhibition, resulting in spheroids with enhanced myocardial differentiation and regenerative abilities, which can be used to treat ischemic heart diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monolayer culture method is used for stem cell therapy, then cell transplantation can be performed, but most transplanted stem cells are killed at the ischemic site resulting in poor therapeutic effect

Engineering Contradiction:
Improvetherapeutic effectVSAvoidcell survival rate
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies spheroidality by culturing cardiac stem cells in a three-dimensional spheroid form rather than traditional two-dimensional monolayer culture. The cells are seeded in a non-adhesive culture vessel that promotes spherical aggregation, creating a 3D structure that better mimics in vivo conditions and enhances cell survival and therapeutic efficacy at the ischemic site.

Inventive Principle:
Principle #14Spheroidality (Curvature)

Solution Approach 2:

The patent transitions from two-dimensional monolayer culture to three-dimensional spheroid culture. This dimensional change allows cells to interact in multiple directions, forming a more physiologically relevant structure that improves cell viability, reduces apoptosis, and enhances the overall therapeutic effect when transplanted to ischemic heart tissue.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Productivity

If monolayer culture is used for stem cell expansion, then culture process is simple, but it is difficult for mass culture and not suitable for clinical treatment

Engineering Contradiction:
Improvemass culture capabilityVSAvoidculture system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

By using non-adhesive culture vessels that promote spontaneous spheroid formation, the patent enables mass culture of cardiac stem cells in a 3D format. This approach allows for scalable production while maintaining cell functionality and viability, making the system suitable for clinical-grade cell preparation without requiring complex culture apparatus.

Inventive Principle:
Principle #14Spheroidality (Curvature)

3Reliability

If stem cells are transplanted to ischemic site, then treatment of ischemic heart disease can be attempted, but high cell death rate makes the treatment ineffective for necrotic tissues

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidcell death rate
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The 3D spheroid structure provides a protective microenvironment that reduces oxidative stress and apoptosis in transplanted cells. The spherical configuration allows for better nutrient diffusion and waste removal compared to monolayer cultures, enhancing cell survival rates when transplanted to ischemic heart tissue and improving treatment effectiveness.

Inventive Principle:
Principle #14Spheroidality (Curvature)

Solution Approach 2:

The patent performs preliminary culture of cardiac stem cells in a 3D spheroid format before transplantation to ensure they are in an optimized state. This pre-conditioning in a physiologically relevant 3D environment enhances cell resilience and survival capabilities prior to implantation at the ischemic site.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS11692171B2Preparation method of human-derived cardiac stem cell spheroid and use thereof
Publication Date: 2023.07.04 HIERABIO INC
  • US11692171B2 patent drawing
  • US11692171B2 patent drawing
  • US11692171B2 patent drawing

AI summary

The present invention relates to a preparation method of a spheroid using human-derived cardiac stem cells and a therapeutic use for ischemic heart disease using the myocardial regeneration effect thereof. The spheroid using the cardiac stem cells provided in the present invention has excellent myocardial differentiation ability and regenerative therapeutic ability as compared to existing cardiac stem cells, and thus may be used for the treatment of ischemic heart disease such as myocardial infarction.