Organs- on-a-chip were initially established at the Wyss Institute for Biologically Inspired Engineering located at Harvard University. The polymer chips containing microtubules are designed to recapitulate the structural, functional and mechanical attributes of human organs and they are only the size of a USB stick (Wyss Institute (2017)).
The chips are not just incredibly cool but also provide an innovative platform for drug discovery, which was recognised by the National Centre for the Replacement, Refinement and Reduction of animals in research (NC3Rs) back in 2012 (3Rs (2012)). The fact that the organs-on-a-chip mimic multiple aspects of the human body means that they could one day be used as an alternative approach to in vivo testing – a controversial but currently essential aspect of drug development.
The lung-on-a-chip, just one of the many organs developed, reconstructs the alveolar-capillary interface of the lung (Huh, D.et al (2010)). A central porous membrane is coated in extracellular matrix proteins that are present in the human lung. One side of the membrane is lined with alveolar epithelial cells isolated from a human lung and human pulmonary microvascular endothelial cells cover the other. The principal compartment allows for air to flow over the epithelial cells and for a blood-like solution containing nutrients to run beneath the endothelial cells. A vacuum on either side of the membrane causes the cells to stretch, in term conveying the movement experienced in the lung when we breathe.
Figure 1: Lung-on-a-chip diagram From Keane, J. (2013)
This model has proven to replicate a lung infection, where white blood cells migrate from the blood-like solution through onto the epithelial side and are observed engulfing bacteria present in the air space using time-lapse fluorescence microscopy (Huh, D.et al (2010)). Small airways-on-a-chip with its goblet and ciliated epithelial cells can be used to model diseases like chronic obstructive pulmonary disease (COPD) and asthma. Addition of interleukin 13 (IL-13) to the epithelium further replicates an asthmatic phenotype inducing goblet cell hyperplasia and cytokine hypersecretion. A paper in Nature has reported to be able to reverse this response with an inhibitor of the JAK-STAT pathway involved in the signalling of IL-13, showing the application of these models in the screening of new treatments (Benam, K. Villenave, R. et al. (2016)).
The next focus is the humans-on-a-chip, which utilize an automated device to connect multiple organs-on-a-chip via a shared vascular network (figure 2). This platform would enable scientist to investigate the pharmacokinetics and pharmacodynamics of a drug in a relevant system (Abaci, H.E. Shuler, M.L. (2015)). Whereby drugs could be administered via the lung-on-a-chip, absorbed by the gut-on-a-chip, metabolised by the liver-on-a-chip and excreted by the kidney-on-a-chip while accessing the efficacy and any toxicity throughout.
Figure 2: Human-on-a-chip schematic From Mok, J. (2015)
An interesting application of this technology is in the scope of personalized drugs. A chip can be developed with an individual’s cell to determine personal response to a drug, providing a tailor made drug with optimal efficacy (Hamilton, G. (2016)). This notion can also be implemented to clinical trials, where potential new drugs could be tested on cells from a certain genetic populations or on cells from children for paediatric medicines. This technology still has a way to go but one day it may transform the drug discovery process.
Blog written by Olivia Simmonds
Abaci, H.E. Shuler, M.L. (2015). Human-on-a-chip design strategies and principles for physiologically based pharmocokinetics/pharmacodynamics modeling. Integr Biol (Camb). 7 (4), 383-391.
Benam, K. Villenave, R. et al. (2016) Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro Nature Methods. 13 (2), 151-157
Hamilton, G. (2016). Body parts on a chip. Available: https://www.ted.com/talks/geraldine_hamilton_body_parts_on_a_chip. Last accessed 20th April 2017.
Huh, D.et al (2010) Reconstituting Organ-Level Lung Functions on a Chip Science. 328, 1662-1668
Keane, J. (2013) The End of Drug Testing on Animals, Lung-on-a-Chip Device. Available: http://www.industrytap.com/lung-on-a-chip-device-to-end-drug-testing-on-animals/2160. Last accessed 21st April 2017
Mok, J. (2015) Organs-on-Chips Emulates Human Organs for Better Biomedical Testing. Available: https://thenewstack.io/organs-on-chips-emulates-human-organs-for-better-biomedical-testing/. Last accessed 21st April 2017
Wyss Institute (2017)Human organs on a chip. Avalible: https://wyss.harvard.edu/technology/human-organs-on-chips/. Last accessed 21st April 2017.
3Rs (2012). 3Rs Prize winners. Available: https://www.nc3rs.org.uk/3rsprizewinners. Last accessed 21st April 2017.