FGF-8 Primed Stem Cells for Cardiac Regeneration

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Solution Overview

Problem

Current therapies for myocardial infarction-induced heart failure are limited, and there is a scarcity of effective and safe compounds for cardiac dysfunction treatment, with the optimal cell type for cardiac regeneration and repair yet to be identified.

Innovation Solution

The use of fibroblast growth factor-8 (FGF-8) and FGF-9 in induced pluripotent stem cells or their conditioned media for enhancing cardiac tissue regeneration and attenuating adverse cardiac remodeling, including the generation of cardiac-induced pluripotent stem cells by expressing stem-cell like factors such as Oct3/4, Sox2, and c-Myc.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cell transplantation is used to repair injured myocardium, then cardiac regeneration is enhanced, but the optimal cell type and treatment efficacy remain uncertain

Engineering Contradiction:

Improvecardiac regeneration efficacyVSAvoidcell type selection flexibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses FGF-8 to alter the differentiation parameters of induced pluripotent stem cells, directing them toward cardiac myocyte lineage. This parameter change in cell differentiation resolves the uncertainty of optimal cell type selection by providing a controlled method to generate the most effective cell type for cardiac repair.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

FGF-8 acts as an intermediary substance that mediates the transformation of induced pluripotent stem cells into cardiac-specific cells. This intermediary approach solves the problem of cell type selection by providing a controllable differentiation pathway rather than directly transplanting undifferentiated or improperly differentiated cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If FGF-8 and FGF-9 are used to enhance cardiac regeneration, then cardiac myocyte differentiation and cell proliferation are improved, but the complexity of the treatment protocol increases

Engineering Contradiction:

Improvecardiac tissue regeneration rateVSAvoidtreatment protocol complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent combines FGF-8 and FGF-9 into a single treatment protocol, merging two growth factors that work synergistically to enhance cardiac regeneration. This combination approach improves productivity by leveraging complementary mechanisms while managing protocol complexity through integrated administration.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent applies FGF-8 and FGF-9 in preliminary stages to prime induced pluripotent stem cells for cardiac differentiation before transplantation. This preliminary action prepares the cells in advance, ensuring they are optimally differentiated and functional, thereby enhancing overall regeneration productivity without requiring complex post-transplantation interventions.

Inventive Principle:

Principle #10Preliminary action

3Productivity

If induced pluripotent stem cells are used for cardiac repair, then cell engraftment and proliferation are enhanced, but the risk of apoptosis and fibrosis remains

Engineering Contradiction:

Improvecell engraftment and proliferationVSAvoidapoptosis and fibrosis

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies FGF-8 and FGF-9 treatment in advance to prevent apoptosis and fibrosis before they occur. By pre-treating induced pluripotent stem cells with these growth factors, the cells are protected against harmful effects during and after transplantation, counteracting potential damage before it manifests.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent converts the potential harm of uncontrolled stem cell differentiation into a benefit by using FGF-8 and FGF-9 to direct differentiation toward beneficial cardiac myocyte lineage. This transforms the risk of improper differentiation into a controlled process that promotes desired tissue regeneration while minimizing harmful outcomes.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentEP2830639B1Methods and compositions using FGF-8 to enhance cardiac regeneration and attenuate adverse cardiac remodeling

Publication Date: 2019.05.08 UNIVERSITY OF CENTRAL FLORIDA RESEARCH FOUNDATION INC

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Figure 2B~2BI

AI summary

In an aspect, the invention relates to compositions and methods for enhancing cardiac tissue and/or cell regeneration. In an aspect, the invention relates to compositions and methods for attenuating adverse cardiac tissue and/or cell remodeling. In an aspect, the invention relates to compositions and methods for inhibiting apoptosis. In an aspect, the invention relates to compositions and methods for identifying a myocardial injury. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.