Researchers at the Harvard Wyss Institute have developed a “body-on-a-chip” consisting of up to 10 organ-on-a-chip devices that are linked together to mimic blood flow between different organ systems. The new system allows for more comprehensive drug testing, enabling researchers to see the effects of a drug on multiple organ systems simultaneously. The Wyss team hopes that the technology could help to reduce the amount of animal testing required for drug development while providing more useful results. In the past decade, numerous organ-on-a-chip devices have been developed. Such technology has the potential to make drug testing cheaper, more convenient, and more accurate than current approaches, which frequently require animal tests. However, to date, such devices have typically mimicked one or two organ systems at most, making it impossible to know the effect of a drug on the entire body. This latest breakthrough from the Wyss Institute involves linking multiple organ chips to form a body-on-a-chip, allowing for more comprehensive drug testing. At the heart of the approach is an automated device termed the “Interrogator,” which can shuttle fluids along channels lined with endothelial cells between numerous organ chips, mimicking blood flow between organs in the body. The Interrogator also has robotic liquid transfer capabilities, meaning that researchers do not have to manually manipulate the system, and an integrated microscope continuously monitors cultured tissues. The Wyss Institute team designed a multi-human Organ Chip system with a human Gut Chip, Liver Chip and Kidney Chip whose vascular channels are linked via a central arterio-venous (AV) fluid mixing reservoir, and whose organ-specific channels are independently perfused. In drug testing experiments, they added nicotine to the lumen of the Gut Chip’s epithelial channel to mimic oral uptake of the drug, and its first pass through the intestinal wall and, via the vascular system, to the liver where it is metabolized, and finally to the kidney where it is excreted. So far, the team has trialed the device in its ability to measure changes in drug levels over time and drug toxicity in specific organs. “We serially linked the vascular channels of eight different Organ Chips, including intestine, liver, kidney, heart, lung, skin, blood-brain barrier and brain, using a highly optimized common blood substitute, while independently perfusing the individual channels lined by organ-specific cells,” explained Richard Novak, a researcher involved in the study. “The instrument maintained the viability of all tissues and their organ-specific functions for over three weeks and, importantly, it allowed us to quantitatively predict the tissue-specific distribution of a chemical across the entire system.” “This is what we love to do at the Wyss Institute: make science fiction into science fact,” said Donald Ingber, another researcher involved in the study. “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.” Source
