The challenge
To obtain significant results when studying cancer therapies, mimicking the human tumor microenvironment is critical if any such results are to be extrapolated to human treatments. In particular, pancreatic tumors present a challenge not readily met by existing models—they contain an excessive extracellular matrix that not only impairs vascularization, but also reduces the ability of T cells and cancer drugs to reach the tumor.
AIM Biotech’s BioAvatar technology provided the solution to effectively examine this problem. In a study published in Biomaterials Science, scientists at Pavesi Lab used AIM Biotech’s idenTx 3D tissue culture chips to create an organ-on-a-chip human pancreatic tumor model that demonstrates the importance of the tumor microenvironment for measuring immune cell infiltration and cytokine production.
Using idenTx to create a pancreatic tumor microenvironment
In a recent work, created a pancreatic cancer model including a vascular vessel and cells that secrete extracellular matrix proteins. They built a human-like pancreatic tumor containing four different cell types:
- The authors injected a human cell line of pancreatic cancer cells, PANC-1, into the central hydrogel chamber to mimic the pancreatic tumors.
- They added Human Umbilical Vein Endothelial Cells (HUVECs) to one of the lateral channels of the idenTx. After two days, these cells formed a monolayer that resembles a blood vessel.
- They seeded human Pancreatic Stellate Cells (PSCs) to the second lateral channel, since these cells are one of the two principal cell types that produce extracellular matrix proteins in pancreatic cancer.
- Once the pancreatic tumor microenvironment was formed on the idenTx chip, the scientists added T cells isolated from human blood to the channel containing the endothelial cells.
Measuring T cell migration and cytokine production on idenTx-modeled pancreatic tumors
The authors measured the migration of T cells from the lateral channel to the central chamber where the 3D-like extracellular matrix containing cancer cells is located. They found that the presence of the endothelial monolayer decreased the migration of T cells as compared to a condition without HUVECs in the lateral channel. This finding highlights the importance of including a vascular structure as an integral component of the model when studying T cell immunotherapy for pancreatic cancer.
The researchers also found that, in general, the production of pro-inflammatory cytokines was dampened by the simultaneous presence of ECs and PSCs on the idenTx chip. This mechanism could help promote pancreatic tumor growth.
Study implications and future use
Overall, this work demonstrates that in order to establish a meaningful in vitro model of pancreatic cancer, specific aspects of the tumor microenvironment not included in previous models are actually of vital importance—and all of this was accomplished by leveraging the unique organ-on-a-chip benefits of AIM Biotech’s idenTx. With this ground broken, the study takes medicine another step closer to the day that such models can benefit individual patients with personalized immunotherapies.