Mesenchymal Stem Cells Expressing TNF-α Receptor Type I

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Solution Overview

Problem

Current treatments for graft-versus-host disease, solid organ transplant rejection, and autoimmune diseases lack effective immunomodulatory solutions to inhibit lymphocyte proliferation and manage immune responses.

Innovation Solution

Mesenchymal stem cells expressing TNF-α receptor Type I (TNFRI) at specific thresholds are used to inhibit lymphocyte proliferation, providing a composition that can be administered to treat various immune-related disorders by modulating immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments are used for graft-versus-host disease and autoimmune diseases, then standard therapeutic protocols are maintained, but effective immunomodulatory solutions to inhibit lymphocyte proliferation are lacking

Engineering Contradiction:
Improveimmunomodulatory efficacyVSAvoidlymphocyte proliferation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses mesenchymal stem cells as an intermediary substance that mediates between the immune system components. These cells express TNF-α receptors and actively modulate immune responses by inhibiting lymphocyte proliferation, serving as a biological mediator to resolve the contradiction between maintaining immune function and preventing excessive lymphocyte activation

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the parameter of TNF-α receptor expression levels on mesenchymal stem cells to achieve optimal immunomodulatory effects. By controlling the expression of TNFRI and other receptors, the patent optimizes the immunosuppressive activity of the cells to effectively inhibit lymphocyte proliferation while maintaining therapeutic safety

Inventive Principle:
Principle #35Parameter changes

2Reliability

If mesenchymal stem cells express TNF-α receptor Type I at high levels, then lymphocyte proliferation is effectively inhibited, but the complexity of characterizing and standardizing cell therapy increases

Engineering Contradiction:
Improvelymphocyte proliferation inhibitionVSAvoidcell characterization complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex functional assays with a simplified receptor expression measurement system. By using flow cytometry or ELISA to measure TNF-α receptor expression levels as a surrogate marker, the invention substitutes complicated immunomodulatory activity testing with a more straightforward quantitative measurement, reducing characterization complexity while maintaining reliability

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention establishes specific threshold values for TNF-α receptor expression (e.g., minimum expression levels required for effective lymphocyte proliferation inhibition). By defining clear parameter thresholds, the patent simplifies quality control and cell therapy standardization, transforming a complex biological activity assessment into a measurable parameter-based criterion

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20240301356A1Mesenchymal stem cells expressing TNF-alpha receptors
Publication Date: 2024.09.12 MESOBLAST INTERNATIONAL SARL
  • US20240301356A1 patent drawing
  • US20240301356A1 patent drawing

AI summary

Mesenchymal stem cells which express TNF-α receptor Type I in an amount of at least 13 pg/106 cells. Such mesenchymal stem cells inhibit the proliferation of lymphocytes and may be employed, in particular, in the treatment of graft-versus-host disease.