Cell Structure for Stroma-Rich Pancreatic Cancer Animal Models
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Solution Overview
Problem
Existing animal models for pancreatic cancer lack sufficient stromal tissue, leading to inaccurate cancer remedy development and limited test substance evaluation, as seen in gemcitabine's ineffective delivery due to fibrotic stroma and poor blood vessel density.
Innovation Solution
A cell structure containing biocompatible macromolecular blocks, cancer cells, and mesenchymal cells is transplanted into non-human animals to create a model rich in stromal tissue, using recombinant gelatin with specific amino acid sequences for enhanced biocompatibility and nutrient delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a cancer-bearing mouse model is used with human pancreatic cancer cells, then cancer remedy development can be performed, but sufficient stromal tissue does not develop and the model does not reflect actual pancreatic cancer state
Solution Approach 1:
The invention segments the tumor tissue into cancer cells and stromal cells, which are then transplanted separately into the mouse model. This segmentation allows for controlled development of stromal tissue while maintaining cancer cell presence, thereby improving the reliability of cancer remedy evaluation by creating a more accurate representation of actual pancreatic cancer tissue composition.
Solution Approach 2:
The invention performs preliminary action by pre-preparing and culturing stromal cells before transplantation. The stromal cells are cultured under specific conditions to enhance their ability to form stromal tissue, and then these pre-prepared stromal cells are transplanted along with cancer cells into the mouse model. This preliminary preparation ensures sufficient stromal tissue development in the final model.
2Quantity of substance
If patient-derived xenograft is used to obtain stromal tissue, then stromal tissue can be formed, but stable amplification is impossible and the number of tests is limited
Solution Approach 1:
The invention uses established cancer cell lines as copies or substitutes for patient-derived cancer cells. These established cell lines can be stably amplified and maintained in culture, providing a stable and renewable source of cancer cells for the mouse model. This copying approach allows for unlimited reproduction of the model while maintaining consistent composition, overcoming the limitation of patient-derived xenografts.
3Reliability
If stroma is fibrotic with poor blood vessels, then cancer cell delivery is blocked, but this fibrotic state prevents effective chemotherapy delivery
Solution Approach 1:
The invention changes the parameters of stromal tissue by controlling the culture conditions and composition of transplanted stromal cells. This results in stromal tissue with improved characteristics, including better blood vessel formation and reduced excessive fibrosis. The parameter changes in stromal tissue composition and structure enable improved deliverability of test substances while maintaining the reliability of chemotherapy evaluation by preserving the stromal barrier function.
Data Source
AI summary
An object of the present invention is to provide a non-human model animal rich in stromal tissue, a cell structure useful for producing the above-described non-human model animal, a method for evaluating a test substance in which the above-described non-human model animal is used, and a method for producing the above-described non-human model animal. According to the present invention, a cell structure is provided which contains a biocompatible macromolecular block and at least a cancer cell and a mesenchymal cell, and in which a plurality of the above-described biocompatible macromolecular blocks are arranged in gaps between a plurality of the above-described cells.