Antigen-Specific Regulatory T-Cell Expansion via MSC Co-Culture
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Solution Overview
Problem
Current methods for preparing immunomodulatory cells, particularly for treating multiple sclerosis, are limited in their ability to generate antigen-specific regulatory T-cells with sufficient immunosuppressive capacity and specificity, leading to suboptimal therapeutic outcomes.
Innovation Solution
A method involving the ex-vivo contact of isolated regulatory T-cells with mesenchymal stem cells in the presence of multiple sclerosis-associated antigens, such as MBP and MOG peptides, to expand and generate antigen-specific immunomodulatory cells expressing markers like CD62-L, FOXP3, and CTLA4, which are then isolated and used for therapeutic purposes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods for preparing immunomodulatory cells are used, then the preparation process is simple, but the ability to generate antigen-specific regulatory T-cells with sufficient immunosuppressive capacity is limited
Solution Approach 1:
The patent combines mesenchymal stem cells with regulatory T-cells in a co-culture system, merging two cell types to achieve enhanced antigen-specific immunosuppressive capacity that neither cell type achieves alone
Solution Approach 2:
Mesenchymal stem cells serve as an intermediary that facilitates the generation and expansion of antigen-specific regulatory T-cells, mediating the immunomodulatory effect through cell-cell interactions
2Reliability
If antigen-specific regulatory T-cells are generated with high immunosuppressive capacity, then therapeutic efficacy is improved, but the preparation method becomes more complex
Solution Approach 1:
The patent performs preliminary expansion and conditioning of regulatory T-cells in co-culture with mesenchymal stem cells before therapeutic administration, preparing the cells in advance to ensure optimal immunosuppressive function
Solution Approach 2:
The patent optimizes culture conditions including cell ratios, cytokine concentrations, and incubation time to maximize the generation of antigen-specific regulatory T-cells with enhanced therapeutic efficacy
3Measurement precision
If non-specific immunosuppression is reduced, then antigen-specificity is improved, but the overall immunomodulatory effect may be weakened
Solution Approach 1:
The patent creates a localized immunomodulatory environment in the co-culture system where mesenchymal stem cells and regulatory T-cells interact specifically with antigen-presenting cells, achieving targeted antigen-specificity while maintaining overall immunomodulatory effect
Data Source
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AI summary
The present invention provides isolated immunomodulatory cells, populations, compositions and therapeutic uses thereof. The immunomodulatory cells of the invention have surprising efficacy in the immunomodulation of multiple sclerosis. In one embodiment said immunomodulatory cells are regulatory T-cells, in a particularly preferred embodiment said immunomodulatory cells are Foxp3+CD4+CD25+ T- reg and/or IL-10/TGF-.beta.- producing regulatory Trl cells. Methods for the preparation, expansion and/or generation of immunomodulatory cells of the invention comprises contacting a cell population comprising of MSC and/or fibroblast cells with PBLs in the presence of one or more multiple sclerosis-associated antigens.