Ex Vivo Tissue Perfusion Platform for Immune Competent Tumor Modeling
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Solution Overview
Problem
Current models for evaluating solid tumors, such as patient-derived xenografts and organ-on-chips, fail to accurately replicate the human tumor microenvironment, lacking a competent immune system and proper stromal and immune cell ratios, which limits the effectiveness of treatment evaluation and customization.
Innovation Solution
A system for ex vivo analysis of resected tissue samples involves mounting a thin tissue portion on a sample platform within a perfusion chamber, where it is perfused with a nutrient-rich solution to maintain a competent immune system and allow for drug delivery and imaging, enabling the preservation of the tumor microenvironment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If patient-derived xenografts are used to model tumors, then the tumor tissue can be studied ex vivo, but the immune system becomes incompetent and stromal cell ratios are altered
Solution Approach 1:
The system segments the tumor microenvironment modeling by using patient-derived organoids that preserve native immune and stromal cells within the tumor tissue structure, rather than implanting into immunodeficient mice. This segmentation allows the tumor tissue to be studied ex vivo while maintaining its native cellular composition and immune competence.
Solution Approach 2:
The invention creates a faithful copy of the human tumor microenvironment by culturing patient-derived tumor tissue in a controlled ex vivo system that replicates physiological conditions. This copying approach preserves the native immune system and stromal cell ratios without the need for murine xenografting, thereby maintaining both tumor model accuracy and immune system competence.
2Ease of manufacture
If standard 2-D cell culture is used, then the model is simple to maintain, but it fails to capture tumor microenvironment interactions and heterogeneity
Solution Approach 1:
The system transitions from 2-D cell culture to 3-D organoid culture, adding a dimensional aspect that enables the tumor tissue to maintain its native architecture and cellular interactions. This dimensional change allows the model to capture tumor microenvironment heterogeneity and cell-cell interactions while remaining relatively simple to maintain through automated perfusion systems.
3Productivity
If tissue is removed from the patient for analysis, then treatment options can be evaluated, but the tissue loses viability and immune function
Solution Approach 1:
The system establishes continuous perfusion of nutrient-rich media through the tissue sample, ensuring uninterrupted supply of oxygen and nutrients. This continuous action maintains tissue viability and immune function over extended periods, enabling comprehensive treatment evaluation while preserving the tissue's physiological state.
Solution Approach 2:
The ex vivo tissue model serves itself by maintaining its own viability through the perfusion system that delivers nutrients and removes waste products. The tissue's immune system remains functional and can respond to treatments without requiring external intervention to maintain basic physiological functions, thereby extending the duration of viable analysis.
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 provides a more accurate and viable tumor model that maintains the native tumor microenvironment, allowing for effective evaluation of treatment options and customization of therapies by supporting the tissue's immune system and stromal components.
Implementation Method 1
flowing perfusate through the perfusion chamber and into contact with the resected tissue portion such that diffusion of oxygen occurs between the perfusate and the resected tissue portion
Data Source
AI summary
Ex vivo analysis can be performed by mounting a portion of live tissue resected from a patient on a sample platform. Using the sample platform, the resected tissue portion can be positioned within a perfusion chamber. Perfusate is flowed through the perfusion chamber and into contact with the resected tissue portion such that diffusion of oxygen occurs between the perfusate and the resected tissue portion. During the flowing, the resected tissue portion maintains a competent immune system. Drugs can be added to the perfusate flow to ascertain the effect on the tissue. The sample platform is designed to be removable from the perfusion chamber for analysis of the tissue by imaging or other investigation techniques, for experimental treatment, or for any other purpose. After removal, the sample platform can be returned to the perfusion chamber for continued viability of the tissue.