For years, disease modeling has relied on animal and cellular models. But these models are often expensive and poorly predict the human responses. Organ-on-a-chip platforms can potentially redefine research by filling these gaps with systems that mimic the physiological interactions within the human body. This article will talk about this novel technology and show you everything you need to get started.
Traditional disease models and their challenges
Researchers typically use animal or cell models to understand how human diseases develop and test new treatments, . Animal models play a critical role in disease pathophysiology dissection and the evaluation of new therapies. Still, they fail to predict many drugs´ efficacy and safety in clinical trials, . Also, the ethical issues involving animal testing have encouraged the search for alternatives. Cell models could mitigate these issues. However, they can´t reproduce the complex interactions between different cell types among tissues and organs inside the human body, .
Modeling diseases with organs-on-a-chip
Organs-on-chips (OoCs) are bioengineered microdevices that mimic the basic functional aspects of organs and tissues. They contain multiple cell types to reflect a physiological balance and the most relevant biomechanical forces to the modeled tissues, .
The main advantage of OoCs over traditional disease models is the ability to control the biochemical and cellular environment to reflect in-vivo responses. Researchers can also vascularize or perfuse tissues, introducing nutrients and fluidic flow to cultured cells. Finally, they can incorporate real-time sensors to monitor the cells’ health and activity, .
A systemic approach to disease modeling
Although our organs are physically separated, they communicate via blood and lymph circulation to maintain homeostasis. Interactions between multiple organs are vital to ensure the body´s functioning, .
For example, the small intestine absorbs digested substances, the liver metabolizes them, the blood circulation delivers them to the target organs, and the kidneys excrete waste products. This complex process of absorption, distribution, metabolism, and excretion influences how our body responds to drugs, .
Besides, many physiological processes depend on regulatory pathways and hormonal feedback loops within the endocrine system. Thus, systemic organ communication is vital to explain and emulate human physiological functions. Furthermore, many diseases like cancer, osteoarthritis and metabolic diseases involve multiple organs, requiring a more accurate systemic approach. For this, researchers have modeled multiple organs in single devices known as multi-OoC platforms, .
Multi-OoC approaches can help researchers find out complex disease´s fundamental molecular mechanisms, . One example is a multi-OoC system that emulates different brain functions. This technology was used to understand the metabolic communication between neurons and microvascular cells of the blood-brain barrier (BBB), .
Another study modeled diabetes type 2 using this approach. Cultures of human pancreatic and liver cells successfully maintained postprandial glucose concentrations in blood while glucose levels remained high in both organ modules when cultured separately, . Multi-OoCs can also be used to study women´s reproductive function and cancer metastasis, among other potential applications, .
What do you need to get started?
As we discussed earlier, OoCs should represent the most relevant biomechanical forces affecting the tissue (such as stretch forces for lung tissues or hemodynamic shear forces for vascular tissues). One way of introducing these forces is through microfluidic channels. These channels can create a fluid flow by delivering cell culture media and removing cell metabolites and detritus, .
Generally, the basic experimental set-up for organs-on-chip include:
Microfluidic chip - helps emulate in-vivo physiological conditions and mechanical forces.
Microfluidic pumps - deliver culture media to your cells. Cellix’s 4U 4-channel Microfluidic Pump is ideal for this type of experiment. This precision pressure pump has a stable and accurate flow rate and enables independent control of 4 different channels, controlling both pressure and flow.
Flow sensors - give you feedback on the flow control to keep experiments on track.
Sample reservoir and other accessories - hold the culture media, deliver drugs, or flow a cell suspension through the organ-on-a-chip system.
Disease model. Nature Portfolio. Available at: https://www.nature.com/subjects/disease-model. Access: 01/03/2022.
McGonigle, P., & Ruggeri, B. (2014). Animal models of human disease: challenges in enabling translation. Biochemical pharmacology, 87(1), 162-171.
Low, L.A., Mummery, C., Berridge, B.R. et al. Organs-on-chips: into the next decade. Nat Rev Drug Discov 20, 345–361 (2021). https://doi.org/10.1038/s41573-020-0079-3
Picollet-D’hahan, N., Zuchowska, A., Lemeunier, I., & Le Gac, S. (2021). Multiorgan-on-a-chip: a systemic approach to model and decipher inter-organ communication. Trends in Biotechnology.
Maoz, B., Herland, A., FitzGerald, E. et al. A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells. Nat Biotechnol 36, 865–874 (2018). https://doi.org/10.1038/nbt.4226.
Bauer, S., Huldt, C. W., Kanebratt, K. P., Durieux, I., Gunne, D., Andersson, S., ... & Andersson, T. B. (2017). Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model. Scientific reports, 7(1), 1-11.