Human Organ Generation via Host IGF1R Knockout
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Solution Overview
Problem
Current methods for generating human organs in animal bodies for transplantation therapy face challenges due to low human cell contribution to animal tissues, with only about 1 human cell in 100,000 animal cells, limiting the regeneration of functional human organs.
Innovation Solution
Genetically modifying non-human animal host embryos by knocking out growth factor receptor genes such as the insulin-like growth factor 1 receptor (IGF1R) or insulin receptor (INR) gene and transplanting mammalian stem cells with wild-type growth factor receptors, resulting in increased human donor cell contribution to host organs, potentially exceeding 95% in certain organs like kidneys, lungs, and thymus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If stem cells are injected into a blastocyst using conventional methods, then a chimeric animal is generated with both donor and host cells in various tissues, but the donor cell contribution to animal tissue is extremely low (about 1 human cell in 100,000 animal cells)
Solution Approach 1:
The patent applies parameter changes by knocking out the IGF1R gene in host embryos, which alters the growth factor signaling parameters. This genetic modification creates a permissive environment that allows donor stem cells to proliferate and contribute significantly to host organ development, transforming the极低 contribution rate into high-level chimerism exceeding 95% in certain organs
2Quantity of substance
If growth factor receptor genes are knocked out in host embryos, then donor cell contribution to host organs is dramatically increased (exceeding 95% in some organs), but the genetic modification process becomes more complex
Solution Approach 1:
The patent employs preliminary action by performing the IGF1R gene knockout in host embryos before injecting the donor stem cells. This pre-modification of the host embryo creates a favorable environment in advance, ensuring that when donor cells are introduced, they can immediately proliferate and contribute to organ development without facing competitive inhibition from host cell growth signals
Data Source
AI summary
Methods of generating functional human organs and tissue in animal bodies suitable for transplantation into human subjects are provided. In particular, the contribution of human donor cells to tissues and organs can be increased in interspecies host embryos by knocking out a growth factor receptor gene such as the insulin-like growth factor 1 receptor or insulin receptor gene. Almost entirely donor-derived functional organs and tissue can be generated by using this method. The methods described herein are useful for generating human organs and tissue in animals and may be helpful for overcoming the current problems with organ shortage for transplantation therapy. Additionally, such organs and tissue can be used in drug discovery, drug screening, and toxicology testing.