“Human-on-a-Chip” OOC to revolutionise preclinical

New system of linked mini-organs heralds a new era of comprehensive drug testing that is faster and more efficient than anything seen before. OOC techniques combined with AI will accelerate discovery.

Preclinical trials can be slow and costly; identifying and excluding toxic effects, finalising administration routes and calculating concentrations all take time and refinement. Enter organs-on-a-chip (OOC).
Longevity.Technology: Drugs need human trials, but the drugs need to be safe enough to test and predicting the way a drug will effect a human body cannot be done with enough accuracy from either animal or standard in vitro testing. Add in the fact that 60-90% of the drugs that are successful in mice trials fail in humans, and there is a pressing need to work smarter, not harder.
Over the last ten years, various organs on various chips have been developed, however, potential drugs are tested in sequence, meaning the process is slow. Now a team from Tel Aviv and Harvard Universities has managed to connect various simulated organs and has shown that they can react to drugs just as human organs would in a clinical trial. Organs included so far include intestine, liver, kidney, heart, lung, skin, blood-brain barrier and the brain.
Tel Aviv’s Dr Ben Maoz said: “We created a unique machine that connects between the nine organs, the brain, the lung, the bone marrow, and others, like a ‘Lego,’ to create a mini ‘Human-on-a Chip’ [1].”

Co-author Professor Donald Ingber, founding director of Harvard University’s Wyss Institute, said: “To solve this massive preclinical bottleneck problem, we need to become much more effective at setting the stage for drugs that are truly promising and rule out others that for various reasons are likely to fail in people [2].”

“This is what we love to do … make science fiction into science fact …”

“This is what we love to do at the Wyss Institute: make science fiction into science fact,” Professor Ingber added. “We hope our demonstration that this level of biomimicry is possible using Organ Chip technology will garner even greater interest from the pharmaceutical industry so that animal testing can be progressively reduced over time [3].”

First the research team developed the “Interrogator”; this is a robotic liquid transfer device that links the individual organ chips and mimics the flow of blood around the body and between the organs in the body. The organ chips have two parallel hollow channels; one is lined with specific organ cells, while the other is lined with vascular endothelial cells that function like a blood vessel. A membrane in between enables the two parts to communicate with each other, exchanging molecules.

OCC explained
Next the team linked the Interrogator with a novel computational model to a series of linked organ chips to test nicotine and cisplatin with successful results. Professor Ingber said. “The modularity of our approach and availability of multiple validated Organ Chips for a variety of tissues for other human Body-on-Chip approaches now allows us to develop strategies to make realistic predictions about the pharmacology of drugs much more broadly. Its future use could greatly increase the success rates of Phase I clinical trials [4].”

Dr Maoz added: “We hope that this platform will enable us to bridge the gap on current limitations in drug development by providing a practical, reliable, relevant system for testing drugs for human use [5].”

In terms of speeding drug development, organ-on-chip (OOC) technology is a key Longevity sector – combined with AI, OOC will dramatically accelerate the drug discovery process. We have covered BIOFABICS’ growth in this area, as well as previous work by the Wyss Institute on using OOC to overcome the tricky Blood-Brain-Barrier.

[1] https://bit.ly/2GNAqKy
[2] https://www.sciencedaily.com/releases/2020/01/200127134724.htm
[3] https://bit.ly/36Y7z0C
[4] https://www.theengineer.co.uk/organ-on-a-chip-wyss-tel-aviv-university/
[5] https://bit.ly/2RVykOV

Image credits: Yonathan Tzhor, Tel Aviv University & Wyss institute, Harvard University