Organs-on-Chips: Applications, Challenges, and the Future
Limitations of current planar, static cell culture systems or animal models result in the high drug failure rates seen in clinical trials, a limitation that can cost pharmaceutical companies billions of dollars. In addition, many human diseases are still unable to be accurately modelled in vitro, limiting understanding and therapy development. These issues highlight the urgent need for more physiologically relevant models of human organs, and have fuelled the development of organs-on-chips.
In theory, organ-on-a-chip devices are aptly named. The engineered silicone modules contain small “organs,” represented by specific types of human cells. Fluid courses through thin channels — like veins, but only a fraction of the size — which interconnect the various cells, and expose them to drug treatments carefully administered by lab scientists. They may look like gadgets from the future, but these organ-on-a-chip devices have already garnered attention from scientists hoping to fix a broken drug discovery process.
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- Organ-on-a-chip and disease-on-a-chip platforms for modeling human physiology and pathophysiology. Reprinted with permission from Elsevier. Citation: Zhang YS, Zhang Y-N, Zhang W. Cancer-on-a-Chip Systems at the Frontier of Nanomedicine. Drug Discovery Today, 2017, 22, 1392-1399.
Within the last decade, scientists began designing organ-on-a-chip devices. The scientific ambition tethered to these devices has been lofty from the start. Scientists promise more realistic pre-clinical results compared to the existing gold standard in labs: traditional in vitro studies. But early iterations of this new technology have had their own limitations, and the way many researchers grow the “organs” may not be as realistic as promised. Recent work out of Harvard’s Wyss Institute addresses this concern. At Wyss, researchers have pioneered a method to develop what may be the most accurate representation of kidney function to-date.
Despite the great promise, creating an organ-on-a-chip system is not a simple process, with a number of obstacles to be overcome. “Challenges include reproducing the architectural complexity of the human tissues and organs in vitro in a miniaturised fashion, and how to link them in the right format (arrangement) that the interconnected systems also recapitulate the human tissue/organ interactions.
However, 3D cell cultures fail to reproduce features of living organs that are crucial for their functions, such as tissue-tissue interfaces (between epithelium and vascular epithelium for example), chemicals or oxygen gradients or the mechanical action of the microenvironment.
Adoption Of OOC Technology By Major Pharmaceutical Companies – OOCs are now being explored worldwide as tools for developing disease models and accurately predicting drug efficacies and toxicities. Many companies and universities have been continuously looking for new and better models for drug development. The advantages of OOCs over cell culture, animal models, and human clinical trials have captured the attention of the medical and pharmaceutical communities focusing on developing targeted therapies. In May 2018, AstraZeneca partnered with Emulate, Inc. to develop OCC models to demonstrate the utility of this technology as a more predictive alternative for efficacy and safety testing of new chemical entities .
Human organs-on-chips (OOCs) are miniaturized versions of lungs, livers, kidneys, heart, brain, intestines and other vital human organs embedded in a chip. With advances in OOC technology, drug regulatory bodies have started testing OOCs for their reliability and their use as an alternative to animal testing.
References:
https://thenewstack.io/organs-on-chips-emulates-human-organs-for-better-biomedical-testing/
https://massivesci.com/articles/futuristic-organ-on-a-chip-stem-cells-kidneys/
https://www.technologynetworks.com/drug-discovery/articles/organs-on-chips-applications-challenges-and-the-future-288031
https://www.theinsightpartners.com/reports/organs-on-chips-market