Organs-on-a-chip: a path towards new treatment modalities


Organs-on-a-chip are tools that can potentially improve traditional drug development and the discovery of new treatments. That's because they help recreate the complex physiology of human organs and provide insights into how different systems interact with each other inside the human body. In this article, we'll see how this technology can lead to the discovery of new treatment modalities. And if you are interested in working with this tool, we will show you the minimum requirements your laboratory should have.


Organs on chips driving human research

Organ-on-a-chip (OOC) platforms mimic specific organ functions in the body providing a more realistic and accurate model for drug testing, [1]. This novel technology could better predict experimental drugs´ safety and efficacy before sending them to clinical trials, [2]. OOCs can be helpful in various applications in both clinical and basic research. We can cite their use as alternatives to animal testing, disease modeling, and the creation of new treatment modalities, [1].


How can OOCs improve disease treatment?

Although there is increasing pressure in the pharmaceutical industry to find better alternatives to drug testing; animal models remain the gold standard in preclinical studies. This lack of human-based models impairs the translation from preclinical data to clinical practice. In this case, OOCs could offer a more accurate prediction of a drug´s safety and efficacy, increasing reproducibility and decreasing the overall cost of a preclinical trial, [2].

Next, we´ll talk about how OOC platforms could help develop new treatments.


Better understanding of disease physiology

OOC systems use advanced microfluidics and cell biology techniques to mimic and control physiological microenvironments. As such, they are more suitable for investigating complex organ and tissue physiology than conventional methods. By characterizing complex physiology, this technology can help understand changes that occur in disease states, [3].

Furthermore, OOCs allow elucidating the mechanisms involved in rare diseases. It also enables the use of patient-derived cells with potential use in personalized disease and progression modeling, [3].


More reliable pharmacological studies

OOCs may provide a reliable way of reproducing new drugs and treatments' pharmacological and clinical responses. With this approach, scientists can integrate multiple organs to provide more realistic estimates of clinical response. Moreover, patient-derived cells could be used to identify response variability on each target organ, [3].


Toxicity assessment

Using OOCs, researchers can predict or characterize the mechanisms of drug toxicity in humans, [3].


Assessing drug-to-drug interactions

OOCs could provide an advanced tool to establish pharmacokinetics and pharmacodynamics parameters essential in drug-to-drug interaction prediction. For example, they could recreate the microenvironment of the human gut, including its mechanical and flow characteristics, to study drug absorption, [3].

OoCs could help assess drugs distribution into specific organs due to their unique flow characteristics. This approach is also advantageous in drug metabolism studies since the conventional methods only evaluate the hepatocytes and don´t explain how other cell types may influence drug clearance, [3].

Finally, kidneys-on-a-chip that mimic the blood and tubular lumen separately could provide better modeling and predictions of renal clearance, [3].


Applications of OOC technology:

  • Evaluation of anti-tumor therapies: In one report, OOC experiments demonstrated the importance of the integrity of the (FPR1)/annexin a1 (Anxa1) in immune cell migration and interaction of cancer cells undergoing chemotherapy-induced cell death, [4]. Cancer cells treated with chemotherapy release Anxa1, a danger signal for immune cells. The OOC system showed that FPR1 expressed by immune cells senses the Anxa1 released by dying tumor cells and migrates towards them, engaging in stable interactions.

  • Identification of antiviral therapeutics: With the pandemic, the need to quickly test antiviral drugs became evident. However, in vitro systems are not ideal in representing the physiology of respiratory organs. So researchers have developed airways on a chip that mimic the epithelium of the bronchi and lungs, [5].

In one study, influenza A-infected airway chips treated with nafamostat combined with oseltamivir doubled the treatment window for oseltamivir. The researchers believe such chips could help speed up the identification of therapies during emergencies, [5].


How to get started with OOCs?

As you can see, organs-on-a-chip are excellent tools with many possible applications in research and development.

However, if you want to get the most out of your experiments, your laboratory must be prepared. Cellix can provide you with a complete set-up (organ-on-chip kit) or just the components you need.

This is what you´ll need to start working with OoCs:

  • Microfluidic chips – to emulate in-vivo physiological conditions and mechanical forces.

  • Microfluidic pumps – to deliver cell culture media. Cellix´s 4U 4-channel Microfluidic Pump is a precision pressure pump with a stable and accurate flow rate that enables independent control of 4 different channels. It allows efficient management of both pressure and flow.

  • Flow sensors – to give you feedback on the flow control, keeping 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.

To learn more about our products or request a quote, please get in touch.


References

  1. Mittal, R, Woo, FW, Castro, CS, et al. Organ-on-chip models: Implications in drug discovery and clinical applications. J Cell Physiol. 2019; 234: 8352– 8380. https://doi.org/10.1002/jcp.27729

  2. Weinhart, Marie, et al. "3D organ models—Revolution in pharmacological research?." Pharmacological research 139 (2019): 446-451.

  3. Isoherranen, N., Madabushi, R. and Huang, S.-M. (2019), Emerging Role of Organ-on-a-Chip Technologies in Quantitative Clinical Pharmacology Evaluation. Clin Transl Sci, 12: 113-121. https://doi.org/10.1111/cts.12627

  4. Mattei, Fabrizio et al. “Oncoimmunology Meets Organs-on-Chip.” Frontiers in molecular biosciences vol. 8 627454. 26 Mar. 2021, doi:10.3389/fmolb.2021.627454

  5. Si, L., Bai, H., Rodas, M. et al. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat Biomed Eng 5, 815–829 (2021). https://doi.org/10.1038/s41551-021-00718-9





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