There has been a pressing call for a viable alternative to animal experimentation because data obtained from animals is irreproducible when extrapolated to humans. Humans and animals have been on their own evolutionary paths for millions of years so they have a myriad of biological differences, such as variations in anatomy, organ function, gene expression, toxin metabolism and immune functioning, just to name a few. Those differences are so intricate that even experiments conducted on chimpanzees, humans’ closest genetic relatives, are unable to accurately predict outcomes in humans.
Often hailed as the future alternative to animal experimentation, Organs-on-Chips (OCs) have a short history dating back a decade ago. It was in February 2010 that an OC replicating a human liver was successfully developed by a group of scientists in America, which enabled them to observe the complete life cycle of hepatitis C. Several months later, in October 2010, an OC capable of simulating liver, intestine and breast cancer tissues, was assembled by a Japanese research team in an attempt to test anticancer drugs.
The development of OCs started to accelerate in March 2013 as the Wyss Institute at Harvard University announced that they would collaborate with Sony Digital Auto Disc Corporation (Sony DADC) so that Sony DADC’s manufacturing expertise could be applied to further advance OCs technologies. Since then, OCs have been fabricated in more than 10 different types, with each replicating a specific human organ. OCs can accurately simulate the biological activities of living human organs due to their unique designs. In each OC, cells configured specifically for an organ are positioned inside tiny tubes of a flexible polymer in order to provide structural support found in our bodies. These cells are also interfaced with a human endothelial cell-lined vasculature, which is composed of microfluidic channels passing through the chip. Because these channels can reproduce blood and airflow inside their flowing fluid, they can supply the cells with oxygen and nutrients, similar to how blood sustains cells in a human body.
Designs of OCs also take the physical microenvironment of living organs into account since mechanical forces will be applied if necessary, such as in case of simulating breathing motions or muscle contractions. As a result, the cells in OCs replicate key functions of their corresponding organs, just as they do in the body, when air, blood and testing compounds, including experimental drugs and cosmetic ingredients, are pumped into the tubes. OCs can potentially overcome their shortcoming of organ isolation when a sufficient number of OCs are connected into a Human-on-a-Chip (HC) in order to physiologically replicate an entire human body. Organs can be linked together via a microfluidic network of culture medium, which circulates in order to act as a blood substitute. This network, in turn, is controlled by an automated instrument, whose role is to manage fluid flow and cell viability. Hence, it is able to provide an efficient systemic supply of nutrients and to remove secreted waste products from all organs. Furthermore, this microfluidic network enables the recapitulation of inter-tissue interactions by facilitating static connection based on physical proximity, or unidirectional perfusion, or recirculating microfluidic flow.
In comparing OCs to animal experimentation, there are multiple attributes that should be scrutinized. Experimenting on animals has the advantage of being in vivo, i.e., experiments are conducted using a whole living organism, which takes the dynamic interrelation amongst organ systems into consideration. However, this testing method fails to consider biological dissimilarities between humans and animals as among drugs deemed successful in animal studies, roughly 85% will fail in clinical trials. Animal experimentation is also prohibitively expensive and time-consuming since testing a single compound can cost up to 1 million USD and require several months to complete.
On the contrary, OCs offer a more affordable and timesaving approach since a toxicity test using an OC is estimated to cost only $22,000 and able to generate appreciable data in less than a month. Another merit of OCs is their close mimicking of human physiological conditions because those chips were fabricated based on real human organs. The only major issue facing OCs is their inability to incorporate inter-organ interactions, but as argued previously, this can be solved by further research in assembling an HC.
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