Mesenchymal Stem Cell Composition for Soft Tissue Repair

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Solution Overview

Problem

Current treatments for soft tissue injuries, such as wounds, are limited by rapid depletion of growth factors, uncontrolled release of growth factors, low cellular engraftment due to hypoxic stress, and lack of biocompatibility, necessitating an improved approach for enhanced repair and regeneration.

Innovation Solution

A composition comprising a substantially pure mesenchymal stem cells population seeded on a biocompatible matrix, specifically derived from adipose tissue and comprising less than 25% fibroblasts, which is undifferentiated and derived from the subject to be treated, providing improved survival and proliferation under hypoxic conditions and enhanced release of pro-angiogenic factors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If local injection of growth factors is used, then growth factors are delivered to the injury site, but the local concentration is rapidly depleted and bioactivity is lost

Engineering Contradiction:
Improvegrowth factor concentrationVSAvoidgrowth factor bioactivity duration
Core Design Contradiction:
Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

The patent uses a biocompatible matrix as an intermediary carrier to deliver growth factors and stem cells to the injury site. This matrix sustains the release of growth factors over time, preventing rapid depletion and maintaining bioactivity. The matrix acts as a mediator between the growth factors and the injury site, enabling controlled and prolonged delivery.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs stem cells that are pre-loaded with growth factors or primed to secrete growth factors upon implantation. This preliminary preparation ensures that growth factors are released in a controlled manner at the injury site, extending their bioactivity duration and preventing rapid depletion.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If direct implantation of decellularized extracellular matrix is used, then native growth factors are delivered, but uncontrolled release occurs and biocompatibility is compromised due to xenogenic origins

Engineering Contradiction:
Improvegrowth factor releaseVSAvoidbiocompatibility
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the origin parameter of the matrix from xenogenic to autologous or allogeneic sources, improving biocompatibility. It also modifies the release kinetics parameter by using engineered matrices that provide controlled release rather than uncontrolled release, ensuring reliable and safe delivery of growth factors.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a biocompatible matrix with specific local properties engineered to provide controlled release of growth factors at the injury site. The matrix is designed with specific porosity, degradation rate, and affinity characteristics that enable localized and controlled delivery, improving both biocompatibility and reliability.

Inventive Principle:
Principle #3Local quality

3Quantity of substance

If differentiated muscle cells are transplanted, then muscle tissue is provided, but cellular engraftment is low due to hypoxic stress

Engineering Contradiction:
Improvecellular engraftmentVSAvoidhypoxic stress
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses stem cells that possess inherent resistance to hypoxic stress and the ability to self-renew and differentiate. These cells can survive and thrive in the hypoxic environment of the injury site without external support, providing self-service capability that overcomes the limitations of differentiated muscle cells.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent changes the cellular parameter from differentiated muscle cells to stem cells, which have different physiological properties including higher resistance to hypoxic stress. This parameter change enables better cellular engraftment and survival in the challenging hypoxic environment of soft tissue injuries.

Inventive Principle:
Principle #35Parameter changes

4Quantity of substance

If non-pure mesenchymal stem cells population is used, then cell quantity is sufficient, but repair and regeneration efficacy is reduced

Engineering Contradiction:
Improvestem cells population sizeVSAvoidrepair and regeneration efficacy
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent extracts and removes non-mesenchymal stem cells from the cell population through purification steps, obtaining a substantially pure mesenchymal stem cells population. This extraction of unwanted cell types ensures that the therapeutic effect is maximized by eliminating cells that do not contribute to repair and regeneration.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the purity parameter of the stem cells population from non-pure to substantially pure (greater than 90% mesenchymal stem cells). This parameter change significantly improves repair and regeneration efficacy while maintaining sufficient cell quantity for therapeutic application.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3294356B1Compositions comprising mesenchymal stem cells and uses thereof
Publication Date: 2021.07.07 UNIVERSITE CATHOLIQUE DE LOUVAIN
  • EP3294356B1 patent drawingFigure 1~2D
  • EP3294356B1 patent drawingFigure 3~4
  • EP3294356B1 patent drawingFigure 5A~6

AI summary

The present invention relates to a composition comprising a biocompatible matrix and a substantially pure mesenchymal stem cells population. The present invention also relates to its use for treating soft tissue injuries.