Smarter drug testing | Replacing Animal Research

The Problem

Understanding how a drug spreads throughout the body and gets taken up by different organs is a vital part of drug development.

Currently, this crucial stage of drug development heavily relies on the use of animals. In 2023, nearly half of all animals and 97% of all rats used in experimental research in Great Britain were for toxicity and safety testing of new pharmaceuticals.

Scientists are making great strides with ‘organ-on-a-chip’ devices. These are clever lab tools designed to mimic a single human organ, like a lung or a liver, in a tiny, artificial environment. They’re already proving incredibly useful for understanding diseases and developing new treatments for individual organs.

However, the human body isn’t a collection of isolated organs. Everything is connected by a complex circulatory system – our blood vessels. There isn’t a truly effective lab system that can accurately show how a drug distributes itself throughout the entire body and how different, interconnected organs react to it, complete with a functioning mini-circulatory system.

This is where the ‘Body-on-Chip’ (BoC) device comes in. It’s a specialised plate that contains multiple tissue cultures, each one simulating a different organ. These mini-organs are then connected to each other through an artificial circulatory system. This innovative device allows researchers to begin seeing how substances might be distributed throughout the body and taken up by different organs.

But there’s a big challenge. The precise environment needed to cultivate and maintain each of these different ‘organs’ within the device is often very different.

For the Body-on-Chip to better mimic a mini-human, it’s essential to:

Make sure there’s no cross-contamination or mixing between these separate environments.

Confirm that each miniature organ truly behaves like the human organ it’s modelling.

The Project

This is what Luisa’s vital project aims to achieve. Her work focuses on creating a standardised, functional cell layer within the BoC device that precisely mimics the natural barriers our own organs have.

These barriers are crucial for maintaining each organ’s unique internal conditions, stopping unwanted substances from getting in, and allowing necessary ones to pass through. Think of it like building tiny, selectively permeable membranes within the chip, ensuring each ‘organ’ stays in its own specific, perfect habitat.

To ensure this barrier truly acts like those in the human body, she will be using special cells called endothelial cells. These cells naturally form the lining of our blood vessels and create many of these barriers. Luisa hopes to observe how these endothelial cells attach and form a strong, selective barrier between the separate cell types within the Body-on-Chip plate.

To test her new barrier, she’ll perform two key measurements:

She will use human serum, the clear liquid part of blood, without blood cells, bound to a dye to see what can pass through this barrier. This will show her if the barrier is selective, just like in a real human.

She will also measure the electrical resistance across the barrier. This is a scientific way to assess how ‘tight’ and complete the barrier is, giving a reliable indicator of its strength and function.

This is an incredibly important part of perfecting the Body-on-Chip technology. Successfully creating and evaluating these barriers will ensure that future research using this device is relevant to human physiology and accurate.

The Potential

If all goes to plan, Luisa’s project will significantly increase the accuracy of the Body-on-Chip device, especially when it comes to understanding how different organs interact within the whole body.

But her work has an even broader impact. After validating this method, Luisa plans to publish her findings. She hopes this will encourage other scientists working on organ-chip devices to adopt these animal-free approaches. This will ultimately reduce the use of animal products in this cutting-edge research.

As the use of these sophisticated Body-on-Chip devices becomes more widespread, having a standardised, effective method for creating these organ ‘compartments’ could be revolutionary. It will increase the reliability and human relevance of the research. Crucially, it will also support further reduction and replacement of animals in drug development and disease research.

The update

In the lab, Luisa managed to get human umbilical vein endothelial cells, a commercially available cell line, to grow on the inserts. Although a full layer of cells across the bottom of the insert was visible through the microscope, she ran into technical issues when staining the cells to give more detailed information. After troubleshooting the issue and choosing a different way of visualising them, she could see full coverage up to all edges of the insert, which means that not only were they not detaching during the staining process, but most importantly, that there was no issue with attaching to the sides of the insert at all.

This confirmed that the endothelial cells have the potential to form a fully functional barrier through the entire area of the insert, which was really promising for the next stage of the research. Luisa went on to demonstrate the formation of the endothelial barrier using immunohistochemistry techniques, but due to technical issues earlier on, did not get the opportunity measure the electrical resistance across the barrier.

Although Luisa’s project didn’t necessarily go the way she had planned it, she nevertheless progressed the development of an endothelial cell barrier for body-on-chip devices. This is going to be vital to ensure that each miniature ‘organ’ behaves like it should in these complex devices that have so much potential to replace animals across so many areas of biomedical science.