Immuno-suppressive Dendritic Cell Production via Shear Stress and UVA
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Solution Overview
Problem
Current methods for producing dendritic cells for therapeutic use, such as in cancer treatment and transplantation, often result in heterogeneous populations with limited viability and effectiveness due to the use of supra-physiologic cytokine concentrations and complex cytokine cocktails, leading to disappointing clinical results and a lack of understanding in differentiating between immuno-stimulatory and immuno-suppressive dendritic cells.
Innovation Solution
A method involving a miniaturized device that applies physical forces and photoactivatable agents like 8-MOP and UVA to differentiate monocytes into either immuno-stimulatory or immuno-suppressive dendritic cells by modulating the expression of molecular markers like GILZ and IL-10, allowing for the preferential production of immuno-suppressive dendritic cells outside the body without the need for cytokine cocktails.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods using supra-physiologic cytokine concentrations and complex cytokine cocktails are used to produce dendritic cells, then dendritic cell production is achieved, but the dendritic cells become heterogeneous with limited viability and effectiveness
Solution Approach 1:
The patent changes the physical parameters of the production method by applying controlled shear stress forces and UVA irradiation instead of using supra-physiologic cytokine concentrations. This physical approach produces more homogeneous dendritic cell populations while maintaining productivity, resolving the contradiction between production efficiency and cell uniformity.
Solution Approach 2:
The patent replaces the biochemical system (cytokine cocktails) with a physical system (shear stress and UVA irradiation). This substitution eliminates the heterogeneity caused by complex cytokine interactions while maintaining effective dendritic cell production, addressing both productivity and manufacturing precision.
2Productivity
If conventional ex vivo production methods are used, then dendritic cells can be produced, but their survival and vigor are inhibited by factors inherent to the production method
Solution Approach 1:
The patent converts the potentially harmful effect of UVA irradiation into a beneficial differentiation signal. By controlling the irradiation parameters, the method induces immuno-suppressive dendritic cell differentiation while enhancing cell survival and vigor, transforming a potential hazard into a therapeutic advantage.
Solution Approach 2:
The patent applies shear stress and UVA irradiation during the early differentiation stage to pre-condition the dendritic cells for optimal survival and function. This preliminary physical conditioning prevents subsequent viability loss that occurs with conventional cytokine-based methods.
3Adaptability or versatility
If physical forces and photoactivatable agents are used to differentiate monocytes, then preferential production of immuno-suppressive dendritic cells is achieved, but the method complexity increases
Solution Approach 1:
The patent segments the differentiation process into distinct controllable stages: monocyte activation by shear stress, followed by immuno-suppressive differentiation by UVA irradiation. This segmentation allows independent optimization of each step, managing complexity while achieving versatile cell type differentiation.
Solution Approach 2:
The patent creates a multi-functional differentiation platform that can produce both immuno-stimulatory and immuno-suppressive dendritic cells by adjusting physical parameters. This universal approach replaces multiple specialized cytokine protocols with a single adaptable physical system.
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 enables the predictable and reproducible production of autologous immuno-suppressive dendritic cells, enhancing their survival and vigor, and allows for targeted therapeutic applications in autoimmune diseases, graft-versus-host disease, and solid-organ transplantation by selectively producing immuno-suppressive or immuno-stimulatory dendritic cells.
Implementation Method 1
subjecting said extracorporeal quantity of said mammalian subject's blood sample to a physical force such that said monocytes are activated and induced to differentiate into immuno-suppressive dendritic cells
Implementation Method 2
photoactivatable agents like 8-MOP and UVA to differentiate monocytes into either immuno-stimulatory or immuno-suppressive dendritic cells by modulating the expression of molecular markers like GILZ and IL-10
Data Source
Figure 1a~1b
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AI summary
The present invention relates to methods for producing immuno-suppressive dendritic cells. The present invention further relates to the use of such cells for treating patients suffering from autoimmune diseases, hypersensitivity diseases, rejection on solid-organ transplantation and/or Graft-versus-Host disease.