Multi organ chip system or in vitro prediction of drug metabolism in vivo

The process of drug development is long and arduous What's more, animal research has attracted a lot of ethical attention in clinical trials It can be said that the development and final approval of modern drugs are greatly dependent on animal models and clinical trials, while a group of scientists have been studying an alternative and more convenient method Recently, scientists from the Harvard's Wyss Institute for biologically inspired engineering have found new ways to solve this "bottleneck" in drug development They integrated 10 human organ chips into an automated system to generate an organ chip platform to study how drugs work in the human body in vitro To some extent, this technology has found an alternative method for animal test and human test Their research results were published in the journal Nature biomedical engineering ▲ the researchers drew the distribution of "organ chips" on Leonardo da Vinci's "vitruans" and used the calculation scale method to convert the data obtained from the drug test on the chip into the organ size of the real human body (photo source: Wyss Institute at Harvard University) The system is called "interrogator" by researchers It consists of 10 different organ chips, including intestines, hearts, lungs, etc the "interrogator" can maintain the function of these organ chips for up to three weeks The aim of this study is to observe the effect of simulated blood flow on the whole system, for example, when screening in the kidney, a drug may appear safe, but may have side effects in other organs So the idea that the researchers designed this system was to detect the risk of side effects as early as possible during drug testing In the end, the researchers conducted two experiments, and the system successfully predicted how the human body metabolized specific drugs In the first paper, the researchers introduced this highly modular on chip platform, which is supported by "interrogator" and assembled by robot system The interrogator transfers fluid between the channels lined with blood vessels in turn, imitating the normal blood flow between different organs of human body In 2010, researchers created the first "lung chip" So far, it has taken them more than eight years to integrate ten organ chips into the "interrogator" Each "organ chip" is the size of a USB and consists of a transparent polymer containing a hollow channel separated by a permeable membrane, including: a channel lined with endothelial cells, the same cells as human blood vessels, and a specific organ cell (such as liver or kidney cells) According to the researchers, the whole machine is installed in a standard laboratory incubator, which can keep living cells under constant temperature and light conditions The second step is to prove whether the system can truly simulate the human environment in drug testing? In order to find out, the researchers used an organ chip with a modular platform to connect the intestine, liver and kidney In the second paper published by the team, we can see the process of "finding the answer" Nicotine gum was studied as an oral drug for neurodegenerative and inflammatory bowel disease, so they added it to the intestinal chip to simulate the process of oral administration When the drug passes through the intestinal wall, through the vascular system to the liver for metabolism, and then to the kidney for excretion, the time when the nicotine gum reaches each tissue and the highest concentration of the drug in each tissue are very close to the previously measured level in the patient Through mass spectrometry, the researchers quantified the exchange between blood and drugs in all different organ chips, as well as the drug content in the vascular channel effluent, and then used the newly developed biomimetic calibration method to fit these data This is the first time for them to combine this calculation method with the experimental data of organ chip, which proves that the "interrogator" system has the ability of drug absorption and metabolism, as well as modeling, and can quantitatively predict the dynamic changes of drug blood concentration (PK) previously observed in human clinical trials ▲ use "interrogator" system to simulate the process of oral administration (picture source: reference [3]) Then, the researchers studied the pharmacological effects of cisplatin, a common chemotherapy drug, which may lead to renal toxicity, myelosuppression and so on They connected the liver, kidney and bone marrow chips to the "interrogator" system Similarly, cisplatin can still be metabolized and eliminated by the kidney and liver, and its level is very close to the patient's internal level The cells in the kidney chips even express the same damage biomarkers as the human kidney during chemotherapy Organ chip platform has been proved to be an accurate, reliable model for preclinical testing "We are keen to turn science fiction into a scientific fact, and we hope that our experimental results will enable the" organ chip "technology to reach the bionic level, so as to attract more people," the researchers said At present, the team is studying the use of its organ chip platform to study intestinal microbiome and influenza transmission reference material: [1] Human Body-on-Chip platform enables in vitroprediction of drug behaviors in humans Retrieved Feb 14, 2020 from https://wyss.harvard.edu/news/human-body-on-chip-platform-enables-in-vitro-prediction-of-drug-behaviors-in-humans/