The new drug development it is a complex and multi-stage process that involves a lot of resources but, above all, a great investment of time and money. Typically, after identifying potential therapeutic targets and developing candidate compounds, the latter are evaluated in cell cultures and animal models to determine its safety and efficacy before proceeding with human clinical trials.
But here’s the problem: both crops and animals have limitations related to their poor ability to mimic the conditions of the human body. On the one hand, the former cannot replicate all aspects of tissue function, that is, they do not behave like the liver, kidney or heart do within the organism. This means that sometimes a drug that works well in the laboratory is not effective when tested in people. With the latter, on the other hand, the small genetic differences between species can be amplified to large physiological differences, since there are differences between the reaction of an animal organism and a human one before the same stimulus.
To address this problem, an alternative is the “organs on chips“, devices the size of a flash drive made from human cells (from the heart, lungs, or brain, for example) that recreate on a very small scale the physical properties of an organ. The researchers believe that, with further development, they may help study diseases and test medicines in conditions closer to real life.
The idea of organs on chips (OoCs for its acronym in English) emerged in the 2000s, when the National Institutes of Health of the United States (NIH) in collaboration with the Food and Drug Administration (FDA) began to finance the development of technologies to create precise models of human organs in the laboratory. Subsequently, the NIH launched a program that aimed to develop 10 different organs on chips within 10 years.
These consist of transparent canals lined with thousands of living cells and pumped with nutrient-containing fluid, or blood, all interacting just as they would in the body. Not only do they mimic blood flow, but they have microchambers that allow researchers to integrate multiple cell types to mimic the diversity of cells normally present in an organ.
In turn, the presence of fluid allows these multiple cell types to connect to study the interaction between them, as well as mimic what a cell experiences in the body, the way it receives nutrients and removes waste, and how a drug will move in the blood. The ability to control the flow of fluids also allowse adjusting the optimal dose for a particular drug.
In 2014, it was introduced the first successful case —that imitated a lung— and consisted of a layer of human lung cells grown on a silicone chip. This chip is able to mimic the expansion and contraction, or inhalation and exhalation, of the lung and simulate the interface between the lung and air. The ability to replicate these qualities made it possible to better study lung deterioration through different factors, and also the response of lung cells to different drugs and toxic substances. As technology advanced, other variations were developed such as the liver, the heart, intestine and kidneys.
Besidesthe current models of OoCs are difficult to use and have some disadvantages: creating them can be very complex and requires a high level of technical skill, they require high investment of money, they require living cells to function (and the availability of human cells may be limited in some cases), as they are living systems their operation can vary between different experiments, which can hinder the reproducibility of the results; They are small systems and may not be scalable to an adequate size for human studies, and their regulation is under development, so it may vary between countries.
In contrast, their advantages are also several: they can improve the safety and efficacy of new drugs before they are tested in humans, they allow studying human diseases under controlled conditions, they can be used to study how different patients respond to drugs (allowing the personalization of treatments, reduce the costs of drug research and development, as they allow testing under controlled conditions before moving on to human studies, serve to study biological processes and interactions between different body systems, and can be used to study rare diseases that are difficult to replicate in animal models.
In summary, organs-on-chips have great potential to improve the safety and efficacy of drugs, study human diseases, personalize treatments, reduce costs, and improve basic and toxicology research.
