Sterilized Multipotent Cell Compositions for Tissue Repair

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Solution Overview

Problem

Current therapeutic methods for tissue repair, particularly in soft tissues like tendons and ligaments, face challenges such as high risk of immune rejection, inconvenience of autologous stem cell use, and inefficiencies in promoting healing and regeneration, including incomplete recovery of pre-injury strength and function.

Innovation Solution

Development of novel compositions comprising sterilized multipotent cells with angiogenic or anti-inflammatory activity, which are irradiated to a dosage of 0.5 to 5.0 Mrad, allowing for allogeneic use without immune response and stored for extended periods with retained therapeutic efficacy, combined with implantable scaffolds for enhanced tissue repair.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If allogeneic stem cells are used for tissue repair, then treatment convenience and scalability are improved, but immune rejection risk increases

Engineering Contradiction:
Improvetreatment convenienceVSAvoidimmune rejection risk
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the problematic immune-responsive components from allogeneic stem cells while retaining the therapeutic beneficial components. This is achieved through fractionation processes that separate cells into different populations, allowing selection of cells or cell components that provide tissue repair benefits without triggering strong immune rejection responses.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses immunosuppressive agents or modulators as intermediaries between the allogeneic stem cells and the recipient's immune system. These intermediaries mediate the interaction by suppressing or modulating the immune response, allowing the allogeneic cells to exert their therapeutic effect without being rejected.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If viable stem cells are transplanted, then tissue regeneration capability is improved, but risk of harmful pathogen transfer and uncontrolled proliferation increases

Engineering Contradiction:
Improvetissue regeneration capabilityVSAvoidpathogen transfer and uncontrolled proliferation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies sterilization methods (irradiation, chemical treatment, or heat treatment) that convert potentially harmful viable cells into beneficial non-viable cells. The sterilization process eliminates pathogens and prevents uncontrolled proliferation while retaining or creating therapeutic components such as growth factors, cytokines, and extracellular matrix that can still promote tissue regeneration.

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

Solution Approach 2:

The patent treats stem cells as disposable, single-use therapeutic agents that are sterilized to eliminate viability. These treated cells are administered to provide their therapeutic effect through their structural components, secreted factors, or immunomodulatory properties, then naturally degrade without risk of long-term uncontrolled growth or pathogen transmission.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Object-affected harmful factors

If high radiation dosage is applied for sterilization, then pathogen elimination is improved, but cell viability and therapeutic activity decrease

Engineering Contradiction:
Improvepathogen eliminationVSAvoidcell viability
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies a controlled, partial level of radiation sterilization that is sufficient to eliminate pathogens but controlled to avoid complete destruction of all cellular components. By carefully controlling the radiation dose, the process achieves adequate sterilization while preserving enough cellular structure and therapeutic factors to maintain beneficial effects.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent changes the parameters of the sterilization process, specifically the radiation dosage, to optimize the balance between pathogen elimination and therapeutic activity preservation. By adjusting this critical parameter, the process achieves effective sterilization while maintaining sufficient cellular integrity for therapeutic benefit.

Inventive Principle:
Principle #35Parameter changes

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

The compositions provide reduced immune response, sustained therapeutic activity, and effective tissue regeneration, enabling improved healing and regeneration of soft tissues like tendons and ligaments with reduced risk of rejection and increased efficacy compared to traditional methods.

Implementation Method 1

sterilized by irradiation, wherein sterilization by irradiation is performed by exposing the composition to radiation at a dosage in the range of 0.5 Mrad to 5.0 Mrad

Methodology Applied
Scientific EffectIrradiation sterilization: Radiation

Data Source

PatentEP3476410B1Compositions and methods for treating and preventing tissue injury and disease
Publication Date: 2021.08.18 MICROVASCULAR TISSUES INC
  • EP3476410B1 patent drawingFigure 1
  • EP3476410B1 patent drawingFigure 2
  • EP3476410B1 patent drawingFigure 3

AI summary

The present invention provides novel compositions comprising multipotent cells, wherein the cells have been sterilized and/or treated to inactivated viruses, and related methods of using these compositions to treat or prevent tissue injury or disease in an allogeneic subject.