TAU studies test drug effects with multi-Organ-on-a-Chip platform
Dr. Ben Maoz.
(photo credit: TEL AVIV UNIVERSITY)
Scientists at Tel Aviv University and Harvard University developed the multi-Organ Chip to improve pre-clinical testing.
Fifty scientists from Tel Aviv University and Harvard University published two studies in Nature Biomedical Engineering on Monday describing their invention of a functioning multi-Organ-on-a-Chip platform that enables in-vitro-to-in-vivo translation (IVIVT) of human drug pharmacology.Dr. Ben Maoz of TAU and Prof. Donald Ingber of Harvard led the studies.The team aimed at solving one of the main issues surrounding drug administration.Only 13.8% of all tested drugs are approved by the US Food and Drug Administration, and preclinical tests – before drugs are tested on humans – are often imperfect. Animals and standard in vitro studies cannot predict human response accurately enough.
“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,” Ingber said.Maoz said: “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.”Organ Chips are “microfluidic devices composed of a clear flexible polymer the size of a computer memory stick that contain two parallel running hollow channels separated by a porous membrane, and independently perfused with cell-type-specific media,” TAU said in a statement.“While one of the channels, the parenchymal channel, is lined with cells from a specific human organ or functional organ structure, the other one is lined with vascular endothelial cells presenting a blood vessel,” the statement said. “The membrane allows the two compartments to communicate with each other and to exchange molecules like cytokines and growth factors, as well as drugs and drug products generated by organ-specific metabolic activities.”The Interrogator is a device that can link individual Organ Chips in a manner that is similar to blood flow between organs in the human body. Through the platform, the researchers tested the effects of the oral uptake of nicotine and of intravenous uptake of cisplatin on different relevant organs.As a result of the studies, they successfully predicted the maximum nicotine concentrations and the time needed for nicotine to reach different tissues.The study also found that “the clearance rates in the Liver Chips in our in vitro-based silicon model mirrored closely what had been measured in patients,” Maoz said. 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,” he added.