NOG Mouse Cancer Model for Human Pathology Mimicry
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Solution Overview
Problem
Current animal models fail to accurately mimic the hierarchical organization of human cancer tissues and the involvement of cancer stem cells, limiting understanding of cancer progression and the development of effective anti-cancer agents.
Innovation Solution
Establishing non-human animal models by transplanting NOG-established cancer cell lines into severely-immunodeficient NOD/SCID/gamma(c)(null) mice, which replicate the hierarchical organization and progression of human cancer tissues, allowing for the observation of cancer stem cell behavior and the assessment of anti-cancer agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional animal models are used, then the model establishment is simple, but the models fail to accurately mimic hierarchical organization of human cancer tissues and cancer stem cell involvement
Solution Approach 1:
The patent uses severely immunodeficient NOG mice as an intermediary host to transplant and maintain human cancer cell lines. This intermediary system allows human cancer cells to grow and form tumors that faithfully replicate human cancer hierarchical organization and stem cell properties, which cannot be achieved in conventional animal models. The immunodeficient state of NOG mice serves as the key intermediary condition that enables human cell engraftment while maintaining cancer tissue architecture.
Solution Approach 2:
The patent changes the immunological parameters of the host animal by using severely immunodeficient NOG mice instead of conventional animals. This parameter change (immunodeficiency) enables the transplantation and long-term maintenance of human cancer cell lines, allowing the formation of tumors that accurately mimic human cancer pathology, hierarchical organization, and cancer stem cell characteristics.
2Measurement precision
If NOG-established cancer cell lines are transplanted into non-human animals, then the hierarchical organization and cancer progression process are faithfully mimicked, but the model establishment becomes more complex
Solution Approach 1:
The patent performs preliminary action by first establishing cancer cell lines in NOG mice before transplanting them into target animals. This two-stage process ensures that the cancer cells are pre-adapted and capable of forming tumors with accurate hierarchical organization and cancer progression characteristics, improving measurement precision while managing the complexity through staged establishment.
3Reliability
If animal models with accurate human cancer mimicry are used, then anti-cancer agent screening and pharmacological effect assessment become more reliable, but the time and resources required increase
Solution Approach 1:
The patent establishes cancer cell lines in NOG mice as a preliminary step before using them for anti-cancer agent screening. This pre-establishment creates a standardized, reliable model system that can be reused for multiple experiments, reducing the overall time and resources required for anti-cancer agent assessment compared to establishing new models for each experiment.
Solution Approach 2:
The NOG-established cancer cell line models serve multiple functions: they can be used for observing hierarchical organization, studying cancer progression, screening anti-cancer agents, and assessing pharmacological effects. This multi-functionality increases reliability across different research applications while amortizing the initial time and resource investment in model establishment.
Data Source
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AI summary
An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.