CD36-Expressing Fibroblasts Regulate ECM Accumulation

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Solution Overview

Problem

Current methods fail to effectively regulate extracellular matrix (ECM) accumulation in the skin, leading to conditions like fibrosis, where ECM homeostasis is disrupted, and there is a need for therapies that can either reduce or increase ECM levels depending on the condition.

Innovation Solution

Administering therapeutically effective amounts of fibroblasts expressing CD36 or agents that shift ECM homeostasis from glycolysis to fatty acid oxidation (FAO) or vice versa to regulate ECM accumulation, using pharmacological agents or cellular therapy to restore the balance between FAO and glycolysis in fibroblasts.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If fibroblasts are administered to increase ECM accumulation for wound healing or regenerative medicine, then ECM levels are increased, but this approach cannot be used for fibrotic diseases where ECM accumulation is pathological

Engineering Contradiction:

ImproveECM accumulationVSAvoidtherapeutic applicability

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent makes the fibroblast population dynamic by inducing phenotypic switching between pro-fibrotic and anti-fibrotic states. Through modulation of TGF-β signaling, Wnt/β-catenin pathway, or metabolic state (glycolysis vs oxidative phosphorylation), fibroblasts can be dynamically reprogrammed to either accumulate or degrade ECM depending on therapeutic needs

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent changes key biological parameters of fibroblasts including metabolic state (glycolysis vs oxidative phosphorylation), signaling pathway activation (TGF-β, Wnt/β-catenin), and phenotypic markers (α-SMA expression) to control ECM accumulation. By altering these parameters, the same cell type can be used for opposite therapeutic effects

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If current methods are used to treat fibrotic diseases, then some ECM reduction may be achieved, but they fail to effectively regulate ECM accumulation and cannot increase ECM when needed

Engineering Contradiction:

Improvetherapeutic flexibilityVSAvoidECM regulation effectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent creates a universal fibroblast-based therapy that can perform multiple functions: increasing ECM for wound healing and regenerative medicine, decreasing ECM for fibrotic diseases, and modulating tissue remodeling. The same cell type and mechanism (phenotypic switching) serve opposite therapeutic purposes, providing multi-functionality

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 effectively reduces ECM accumulation in fibrotic conditions by promoting a catabolic phenotype in fibroblasts, enhancing ECM degradation, and can increase ECM accumulation as needed, offering a therapeutic strategy for managing ECM-related diseases and regenerative medicine.

Implementation Method 1

an agent capable of shifting ECM homeostasis from glycolysis to fatty acid oxidation (FAO)

Methodology Applied

Scientific EffectFatty acid oxidation: Oxidation

Implementation Method 2

fibroblasts which express CD36

Methodology Applied

Scientific EffectFatty acid transport: Absorption (physical)

Data Source

PatentUS11819535B2Composition and methods for regulating extracellular matrix accumulation

Publication Date: 2023.11.21 UNIV HEALTH NETWORK

AI summary

There is described herein methods of treating a disease associated with extracellular matrix (ECM) in a patient. In some cases, the methods comprise administering to the patient a therapeutically effective amount of fibroblasts which express CD36.