Ex Vivo Perfused Human Organs for Toxicity Testing
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Solution Overview
Problem
Current methods for assessing the effects of substances on humans are inadequate, relying on non-human animal studies which can lead to false positives and negatives, and lack directness and relevance to human physiology, particularly in evaluating hormone-disrupting and toxic effects.
Innovation Solution
The use of perfused human-derived organs and tissues, specifically those unsuitable for transplantation, to evaluate the effects of substances by perfusing them with a medical fluid containing the substance and analyzing the organ's response, providing more direct and clinically relevant data on absorption, metabolism, elimination, and toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-human animal studies are used to assess substance effects, then testing can be performed without direct human exposure, but the results may lead to false positives and negatives and lack relevance to human physiology
Solution Approach 1:
The patent uses ex vivo human organs and tissues as an intermediary system between non-human animal testing and direct human in vivo studies. This intermediary approach allows substances to be tested in a human biological context without exposing living humans to potential toxins, thereby maintaining both safety and physiological relevance. The human organs retain their native architecture, cell types, and physiological functions, providing accurate data on human-specific metabolic pathways and toxicity mechanisms.
Solution Approach 2:
The patent creates a functional copy of human organ systems using ex vivo perfused organs and tissues. These copied organ systems maintain the essential physiological functions and biochemical pathways of human organs, allowing researchers to study substance effects in a controlled environment that replicates human biology without the risks of in vivo human testing.
2Measurement precision
If in vitro tissue preparations are used to assess substance effects, then direct human tissue can be studied, but the farther the tissue is from the whole organism, the greater the risk of false positives and false negatives
Solution Approach 1:
The patent merges the advantages of in vitro control with in vivo physiological relevance by combining human tissues with their native vascular supply and circulatory system in an ex vivo perfusion setup. This integration maintains the complete architectural and functional context of the organ while allowing controlled substance administration and sampling, thereby eliminating the false positive/negative issues associated with isolated tissue preparations.
3Adaptability or versatility
If healthy organs are used for testing, then the organ function is preserved, but the testing cannot evaluate effects in the context of pre-donation disease or injury
Solution Approach 1:
The patent applies local quality by maintaining the specific disease state or injury condition of each organ while performing the toxicity testing. Rather than using uniformly healthy organs, the approach preserves the local pathological characteristics (such as fibrosis, inflammation, or functional impairment) that are relevant to the specific clinical question being investigated, thereby enhancing the translational value of the results.
Data Source
AI summary
Properties such as toxicity of substances may be determined by assaying properties, fates and effects of substances in an ex vivo metabolically active human organ or tissue under normothermic perfusion with a fluid containing a test substance. The data can be used as, for example, part of a submission to a government regulatory organization. Preferred methods use perfused endocrine gland organs or tissues to evaluate hormone or other bodily chemical disruption caused by substances and pre-donation diseased or injured organs or tissues.