What does the future look like for your work with Organ-Chips?
Emeli: To fully capture the intricate renal cellular ecosystem and understand potential mechanisms of renal injury, a more comprehensive transcriptional analysis is needed, incorporating a wider range of cell types (such as renovascular cells and pericytes) and advanced technologies like single nucleus RNA-Seq in complex chip systems.
How do you decide when to use Organ-Chips rather than conventional research models for your work?
Emeli: Organ-on-a-Chip models excel in simulating human-like physiology, making them ideal for studying drug effects, disease mechanisms, and tissue interactions with high accuracy, particularly in early drug development. While traditional cell cultures and animal models are useful for initial screening, understanding basic cellular mechanisms, and validating Organ-on-a-Chip findings in a whole organism context, Organ-on-a-Chip models offer a more physiologically relevant approach to predicting human responses.
What is the concentration of PBMCs used in the duodenum versus colon case study? As the liquid flushes through the chips, how do you maintain constant circulation?
Ben: The PBMCs were dosed at a concentration of 4 x 106 cells/mL for 10 minutes through the top channel of the chip. After this, the chips were visually inspected and put back on flow. You can find a link to the protocol here.
Emulate has since improved upon this workflow, using a buoyancy media which keeps the immune cells evenly distributed in the media suspension for a greater amount of time. Using this updated protocol, we administer immune cells in the vascular channel for up to 4 hours at a media flow rate of 1,000 µl/h.
How do you see organoids vs. Organ-Chips in terms of their application for toxicity and efficacy studies?
Ben: Both are valuable tools in a researcher’s tool kit—it just depends on the questions being asked. For evaluating drug candidate toxicity and efficacy, it will depend on the drug target and expression levels in each case.
We have demonstrated in multiple studies that cells experience greater levels of differentiation and maturation in Organ-Chips compared to other culture methods. Additionally, certain targets are found to be uniquely expressed in Organ-Chips that are not in organoids or other models (animal or in vitro).
The efficacy question is also enhanced with Organ-Chips, due to the dynamic chip microenvironment which affects cellular behavior. For example, in vivo there is constant blood flow and perfusion, and so drug dwell time happens in a dynamic setting, not under static conditions where secondary or tertiary metabolites wouldn’t play such a role in vivo as they can in standard 2D or 3D culture systems. This can increase the human relevance of efficacy studies performed on-chip compared to organoids.
However, organoids and Organ-Chips can work very well together, and scientists do not need to chose just one or the other. We find that many researchers might use organoids for higher-throughput studies, and then use Organ-Chips when greater complexity and human relevance is required.
Does Emulate have experience with skin disease? With eye disease?
Ben: These are both areas of rapidly growing interest, Emulate does not have direct experience in skin and eye disease at this time. However, if you would be interested in discussing more, we would be happy to connect and see how we can best support your research efforts.
