We stumbled upon something extremely interesting just a few weeks ago: Organs-on-chips! These chips are like a greenhouse for cells, providing an artificial microenvironment for cells to grow and just like small plants, they need the right environment to grow well.
Traditionally, artificially grown cells did not function in a petri dish as they did within the human body. This is mainly because cells need the right intercellular and environmental interactions to develop to their full potential. But Organs-on-chips (OOC) models got it covered, and they are looking to disrupt the current state of affairs in the industry.
Pharma is having hard time
The pharmaceutical industry is struggling with low success rates when bringing drugs to the market. The process is painfully slow, it often takes more than a decade and with costs reaching USD 2 billion. The pharmaceutical industry is waiting eagerly for new and efficient ways to conduct clinical trials. Some of the biggest reasons for the low success rates are non functional in vitro models and non predictive animal models. These models simply cannot completely predict whether the drug will have a favorable effect on humans and whether the drug is absolutely safe. Thus, carefully evaluated clinical trials are needed and often, the tested drug candidate proves to be a rotten egg. Furthermore, the variety of human genetics and phenotypes adds an extra spice to this cocktail. But, there are new solutions coming up such as, organ-on-a-chip technology!
This short video explains how OOC were invented:
OOC have the look and the talent!
So far, there are organs-on-chips models for multiple tissues/organs, such as the heart, kidney, neuron, liver and blood vessels. These models have given insights about how the human body works. Interestingly, for example, liver cells survive longer in the OOC models than in the traditional in vitro model, just as plants in a greenhouse versus potted plants.
OOC are also a promising technique to create disease models. There are already models for inflammation, cancer and neurodegenerative diseases. These OOC models hold great promise to understand the tissue biology of different diseases, as this is the first instance when a physio-chemical environment can be willfully modified and its effects analyzed; not to mention, the specific tissue-drug interactions. Even more, OOC models allow real-time imaging, which wasn’t possible before, for example, seeing how lymphocytes start gathering to the location of infection in real time!
OOC models not only look cool but also have the potential to replace traditional cell cultures and animal models.
A chip for you, a chip for me…
For a long time, the pharmaceutical industry has been speaking about personalized medicine and yet only a few products are out there. Still, the dream of personalized medicine is here and with the OOC and other current technologies in the medical field, we might be a step closer to making it a reality. Perhaps in the future, drug trials will be conducted for “genetic groups” and unpleasant surprises of safety and efficacy could be avoided. Perhaps, the time will come when your doctor prescribes you drugs that have been tested with your own cells on the OOC models. Even more, OOC could be a platform for growing high quality cells for you in the case of an accident. This could lead to better clinical treatments, especially for injures in which the cells have very limited reproductive potential, such as cardiac and cartilage injuries.
As humans consist of several different organs which are continuously interacting with each other, researchers and existing OOC companies have been developing multi-organ-chips (aka human-on-a-chip or HOC)! These chips are connected to each other through microfluidic devices and mimic the natural way that organs are connected in the human body. The purpose of such devices is to replicate the way human metabolism works and thus, provide a deeper understanding of drug testing and disease etiology. If OOC models seem promising, we’d argue that the human-on-a-chip concept is revolutionary.
Nothing is perfect
Yep, it’s never easy being disruptive. Many challenges still need to be addressed for OOC and HOC models. Even though, these models hold a great promise to do real-time examinations, it’s far from being done in real life. Many of the analyses are still invasive and this disrupts the OOC model. Followingly, the OOC-model assessments often remain time-consuming and require significant expertise, not a very convenient combo for everyone…OOC models have low cell count which make the analyses difficult to execute; quite often the concentration of secreted products needs to be relatively high so that it can be analyzed with current techniques. This makes it tricky to analyze the metabolites of the OOC models, as the concentration of the metabolites is too low due to the low cell count and continuous perfusion.
Building OOC models is tricky. It is difficult to get the different types of cells in the right places and reach the right physicochemical environment. However, the 3D bioprinting processes have been introduced to address this problem and have been successful in creating a liver-on-a-chip.
Worth being excited?
A big yes!
Even though the OOC models are still a work in progress, it’s clear that they have the potential to disrupt the development of drugs and medical devices by leading the way to the identification and understanding of biomarkers and molecular mechanisms of diseases. Who knows, maybe the OOC models could also become a suitable environment for tissue culture in the replacement of injured tissues!
Obviously, both OOC and HOC models are still a simplification of the human body, but they are deemed more effective than traditional in vitro models and they are expected to be more accurate than animal models. Many of the big pharma companies are already testing these models, such as Janssen and AstraZeneca! We are expecting further news from this field!
Credits for A-W-E-S-O-M-E co-authors Kristal M and Sushrut S!