New Experimental Models for Drug Screening
26 September 2018
Blog by Elaine Lima de Souza, Ph.D.
Billions of dollars are spent in drug screening and development of new medicines. However, about 90% of the drugs fail when reaching phase 1 of the clinical trials or show unpredicted side effects. Therefore, efforts are needed to create new experimental models for drug screening.
Animal models are gold standard for biological tests. However, sometimes the results are not representative for the effects found in humans. Furthermore, the willingness to stop with the use of animals in research also adds reasons to find new models to study human diseases and to use them for drug screening.
New trends in biotechnology are bringing great models in drug development which include organoids and organ-in-a-chip.
Organoids are clusters of cells constituted by different cell types that can organise and communicate similar to an organ. Those organoids are created from embryonic stem cells or induced pluripotent stem cells (iPS). They are so similar to a real organ. For example, a cardiac organoid is able to beat such as a heart and a pancreas organoid can produce insulin.
One of the great advantages of the use of organoids is that patient cells can be used to generate the organoids and the effects of the drugs can be better addressed, in a very personalised manner. It will reduce the amount of money spent on non-effective drugs and also save money on drug development.
When we talk about an organ, we must remember that it is not just a bunch of cells together, but an organised system with a very detailed tridimensional architecture. The establishment of a better environment for the cells is very important and has been made possible with the use of 3D bioprinting and bioink. Bioinks are “printed” in microchips or microreactors in which physiological reactions will take place. It is known as organ-in-a-chip and they are an interesting tool to study the effects of drugs in human organs.
Besides the technological advances reached so far for the creation of organoids and organ-in-a-chip, an important question is still arising: Can those systems be integrated in a physiological manner?
An integrated organ-in-a-chip was first reported in 2017 in the NATURE Scientific Reports (1). It was developed as an integrated platform of three organs-in-a-chip: heart, liver and lungs. It is a complex system of microreactors interconnected with microfluids allowing the interaction of those systems.
Authors have shown the advantages of this platform by treating the system with different drugs. For example, treatment of the cardiac organoids with propranolol caused cessation of the beating in the cardiac-only system, but when connected with the liver no effect was observed, indicating metabolisation of propranolol by the liver, that was confirmed using mass spectrometry.
Nevertheless, the most exciting result was the observation of an unexpected side effect of a drug. Bleomicine is used in the treatment of cancer and has side effects of lung fibrosis and inflammation. In the three organ systems the treatment with Bleomicine stopped with the cardiac organoid heart rate. But when Bleomicine was administered in the cardiac-only system no effect was observed. The scientists believe that Bleomicine is inducing the formation of a secondary factor that affects other organs in the platform. The unexpected side effect of a drug is a discovery that can only be addressed with the multi-integrated platform.
Organoids, organ-in-a-chip and multi-integrated platforms are very promising, not only in scientific research, but also as new models for drug screening. Those innovative technologies will save billions of dollars in drug development, will bring a more personalised medicine, and will contribute to stopping with the use of animals in research.
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(1) Skardal A. et al, Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Nature Scientific Reports.