Unlike other microphysiological systems on the market, Aracari’s platforms offer human 3D tissues which are uniquely nourished by living, perfusable blood vessels. We generate such tissues by reproducing the native vascular environment (endothelial cells, stromal cells, and extracellular matrix) then combine these vessels with other tissues of interest, such as various tumors or blood-brain barrier components. As a result, Aracari offers a novel platform that is uniquely suited to reproduce delivery of your therapeutic in a way that matches what happens in the body.
From a design perspective, Aracari’s platform is comprised of optically clear plastic. This allows for robust data collection using non-invasive imaging techniques over multiple timepoints. This ensures you get the maximum amount of data from each micro-tissue over the course of your study. Lastly, since we use microfluidics technology to build these tissues, flow volumes are small (tens of microliters), ensuring that only minimal amounts of valuable testing compounds are required for each study.
All tissues in the body are within the width of a human hair from a blood vessel. This location is critical for delivering nutrients and removing waste from these tissues. Consequently, almost all drugs and therapies are delivered to tissues through blood vessels, making them a critical component for accurately modeling drug delivery in the human body.
We have tested many different immortalized tumor cell lines and types within the VMT™, including tumors originating from colorectal, breast, melanoma, pancreatic, and lung cancers. Although these specific tumor types have been tested most extensively in our platform, we have not had any tumor types fail to grow. If your tumor of interest is not listed, please reach out to our team to discuss adding this tumor for your next study.
Aracari’s blood vessels are self-assembled from endothelial cells and a surrounding matrix remodeled by neighboring stromal cells. As a result, our blood vessels mimic the flow rates, permeability, and gene expression of blood vessels in the body.
Since Aracari’s system relies on gravity-driven flow, flow rates can be modified simply by altering the volume in the medium reservoirs. This allows us to test a wide variety of physiological flow rates to best mimic the shear and flow characteristics required for your study.
Many studies utilize 2D kill curves to determine IC50 concentrations – the drug concentration needed to kill 50% of the tumor cells. However, these drug doses are not necessarily the same as those necessary for dosing patients since tumor cells in a petri dish are bathed in drug and therefore require less drug to kill the tumor cells.
IC50 concentrations determined in Aracari’s 3D platforms can often differ quite substantially from those seen in 2D cultures. Importantly, however, the Aracari platform better mimics drug delivery in the human body, yielding more informative drug dosing information.
Conventional drug study techniques, such as tumor monocultures or tumor spheroid cultures are unable to fully reproduce the environment of tumors in the body. For example, 2D cultures are usually comprised of single types of cells growing on a hard plastic – an environment that neglects tumor cell interactions with neighboring cells/matrix and also requires that tumors grow on an unnaturally stiff substrate that is not found in the human body. Spheroids partially solve these problems by allowing different cell types to aggregate and interact with one another. However, tumor spheroids remain bathed in growth medium, relying on diffusion of nutrients (and drugs) to reach tumor cells within the spheroid. Additionally, some tumors, particularly those that are metastatic, do not readily form cohesive spheroids. As a result, spheroid studies with these types of tumors are often impossible.
Aracari’s 3D platform allows tumors to form within the matrix, interact with other cell types, and be fed by blood vessels, thus allowing drug studies to commence, even with difficult-to-model metastatic tumors.
Aracari’s VMT™ contains vessels surrounded by stromal cells (pericytes) and extracellular matrix. Tumors are embedded within this matrix outside of the vessels and induce several changes to the environment that are characteristic of tumors in the body, including disrupting the vessel basement membrane and locally-inducing leak (permeability) from vessels. As in the body, this induced permeability can be reduced with vessel stabilizers, such as VEGF blocking antibodies like bevacizumab.
Yes, we have observed differential responses of tumor subpopulations to various therapeutics. These differences result from tumor cell heterogeneity in our platform, as determined by single-cell RNA sequencing.
We have successfully tested many types of therapies in Aracari’s platforms for our clients, including small molecules, antibodies, antibody-drug conjugates, encapsulated RNA, viruses, and various T cell populations (e.g. T cells, CAR-Ts, gamma-delta T cells, etc.).
Aracari’s platforms contain up to 16 tissue units arrayed on a standard 96-well plate. This allows for simplified, semi-high-throughput studies aimed at side-by-side comparison of different drug compounds or different tissues with appropriate replicates.
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