Humanized Mouse Model for Skin Immune Research
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Solution Overview
Problem
Current humanized mouse models for studying skin-related diseases and immune responses are limited by structural differences between human and mouse skin, lack of direct correspondence between cutaneous T cell populations, and interference from host immune cells, making it difficult to study specific immune cell functions and interactions within the skin tissue.
Innovation Solution
A non-human mammalian model is developed by engrafting a neutrophil-depleted immunodeficient host, such as an NSG mouse, with a human skin equivalent and human immune cells, allowing for the study of human skin homing and resident immune cells without interference from host immune responses, using grafting chambers to create an organotypic human skin equivalent and engrafting human immune cells like T cells, B cells, and dendritic cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional animal models are used for skin research, then the model is simple and easy to maintain, but the structural differences between human and mouse skin make the research results not directly applicable to humans
Solution Approach 1:
The model segments the immune system by using immunodeficient mice that lack functional immune cells, allowing separate engraftment of specific human immune cell populations. This enables researchers to study individual immune cell types or combinations without interference from host immune cells, directly addressing the reliability issue while maintaining manageable complexity through modular cell addition
Solution Approach 2:
The patent uses immunodeficient mice as an intermediary host that provides a living physiological environment without functional immune interference. The host mouse serves as a bridge between in vitro human skin models and in vivo human studies, enabling reliable human skin research while the simplicity of mouse handling maintains ease of operation
2Reliability
If humanized mouse models with human immune cells are created, then the study of human immune responses is improved, but the interference from host immune cells and structural differences still limit the study of specific immune cell functions
Solution Approach 1:
The patent extracts and removes the interfering element by using immunodeficient mice that lack functional immune cells. This creates a clean background where only the engrafted human immune cells are present, allowing straightforward study of specific immune cell functions without the complexity of distinguishing host versus graft immune responses
Solution Approach 2:
The model applies local quality by engrafting human immune cells specifically into the skin equivalent tissue, creating a localized human immune environment within the skin while the rest of the host remains immunodeficient. This allows focused study of cutaneous immune responses without systemic immune interference
3Adaptability or versatility
If complete human immune system is engrafted, then the immune response study is comprehensive, but the complexity of analyzing interactions between multiple immune cell types increases
Solution Approach 1:
The patent applies dynamics by making the immune system composition adjustable and flexible. Researchers can dynamically modify which human immune cell types are engrafted based on specific research questions, allowing comprehensive studies when needed while simplifying to specific cell types when focusing on particular functions, thus balancing versatility with analytical complexity
Data Source
AI summary
A non-human mammalian model for human diseases or disorders comprising a non-human neutrophil depleted mammalian host engrafted with a human skin equivalent (huSE) and human immune cells.