Human Avatars — a sustainable alternative to drug testing on animals
Chronic human disease such as diabetes and cancer affect the body as a system rather than targeting individual organs. Drugs and various therapeutic compounds (e.g. nutraceuticals, probiotics) introduced into the human body also interact with a host of different organs. These interactions determine their therapeutic effectiveness or adverse side effects.
Currently, researchers often rely on animal models to predict how the human body reacts to drugs since animals can capture the entire physiology of the organism as opposed to simplistic cell cultures that are only representative of one single organ.
However, animal testing is not sustainable due to cost and ethical issues. More importantly, animals such as mice and rabbits do not always accurately predict human responses and can lead to drug failure with devastating and costly consequences.
Our approach / Research focus
The Micro-Tissue Engineering Laboratory aims to combine organs-on-chip technology with data science to create human avatars that can accurately predict complex drug responses as an alternative to animal testing.
We engineer artificial systems to mimic multi-organ functions and interactions by recapitulating biological functions and processes and integrating them into miniaturised, scalable platforms.
Then we use multi-metric data measurement to validate the accuracy of the human avatar systems with clinical or in vivo responses.
Research Outcomes / Real-world impact
Predicting drugs that cause skin sensitisation side-effects
There is no way to identify drugs that potentially can cause life-threatening skin reactions, since drug-induced skin sensitisation is caused by the complex interactions between the liver, the immune system and the skin.
The drugs need to be biotransformed by the liver into reactive chemical species that can either directly cause the epidermis of the skin or indirectly activate the immune system to attack the epidermis.
We have developed a novel multi-culture array which enables the coculture of the liver, immune and skin cells in their respective microenvironment while allowing their interactions via soluble factors including drug metabolites.
This makes it possible to simultaneously measure five readouts that represent the different mechanisms involved in the skin sensitisation reaction. The five readouts are integrated with a machine learning algorithm that helps us to classify whether the drug is a skin sensitiser.
Mimicking how probiotics can modify human body functions
Microbes, known as the microbiome, that coexist in the human body are recognised as important for health and diseases. Researchers are developing probiotics as a form of therapy to treat diseases or enhance body functions. However, testing the safety and efficacy of probiotics in germ-free mice is costly and time-consuming.
We have successfully developed a multi-organ human avatar system. The Lego-like modular platform connects different organ chips and allows them to interact. Individual units can house bacteria such as probiotics in the liver, gut, neurons, tumour cells etc to mimic various microbial-host interactions and find connections between the gut and the brain or the gut and the liver.
We are researching modulating brain cognitive functions through the gut microbiome to test specific bacterial strains’ impact on neuronal functions. In collaboration with National University of Singapore, Synthetic Biology for Clinical and Technological Innovation (SynCTI), we have also shown that the effects of fatty liver can be reversed.
Predicting chemotherapy responses in colorectal cancer patients
Not all colorectal cancer patients respond to the same type of chemotherapy. The best way to predict which cancer treatment will work is therefore to test them directly on the patient’s tumour.
Traditionally, this involves grafting a piece of the patient’s tumour in immunodeficient mice and testing different chemotherapies on the animals.
We have created human avatars of colorectal cancer patients by taking the patient tumour cells and growing them in a multiplexed microfluidic device which can simultaneously conduct 32 drug testing conditions. This confirmed that patients respond differently to chemotherapies, but more importantly, testing treatments in the human avatar devices was more than seven times faster and predicted the outcomes as accurately as testing cancer treatments in mice.
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- Ong, Louis Jun Ye, et al. “Comparative study of tumour-on-chip model with patient-derived xenografts for predicting chemotherapy efficacy in colorectal cancer patients.” Lab on a Chip (Manuscript under review)
- Chong, Lor Huai, et al. “Engineering and measuring systemic multi-organ interactions for translational applications.” Proceedings of the 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS). Chemical and Biological Microsystems Society, 2020.
- Tan, Hsih Yin, et al. “Assessing gut microbiome-liver crosstalk with a modular microfluidic platform.” Proceedings of the 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS). Chemical and Biological Microsystems Society, 2019.
- Ong, Louis Jun Ye, et al. “Self-aligning Tetris-Like (TILE) modular microfluidic platform for mimicking multi-organ interactions.” Lab on a Chip 19.13 (2019): 2178-2191.
- Chong, Lor Huai, et al. “A liver-immune coculture array for predicting systemic drug-induced skin sensitization.” Lab on a Chip 18.21 (2018): 3239-3250.