Novel vascularized cancer-on-a-chip model reflects the microenvironment of liver tumors

Dr. Vadim Jucaud's lab at the Terasaki Institute has developed a human vascularized liver cancer-on-a-chip model to evaluate vessel remodeling and cell death in response to embolic agents. This novel platform reflects the microenvironment of liver tumors, particularly a functional and perfusable microvasculature that can be embolized. This powerful in vitro tool aligns with the National Institutes of Health (NIH) efforts to reduce animal testing and promote alternative methods, including microfluidic devices that mimic human organs.

Embolic treatment for liver cancer is a minimally invasive therapy delivered through a catheter into the hepatic artery to block tumors' blood supply and starve them of oxygen and nutrients. This approach can be combined with chemotherapy or radioactive beads to enhance its effect. However, the development of novel embolic agents is often optimized in animal models, which differ significantly from humans at the cellular, tissue, and organ levels.

A vascularized cancer-on-a-chip offers a human-relevant, ethically sound alternative to animal testing, aligning with the growing push for non-animal technologies in preclinical drug development."

Dr. Vadim Jucaud, Principal Investigator

To bridge this gap, Dr. Jucaud's lab developed a vascularized embolization-on-a-chip model that replicates the microvascular networks of liver cancer. This platform incorporates a tumor spheroid surrounded by perfusable capillary-mimicking blood vessels in a microfluidic organ-on-a-chip system. To mimic the embolization of the hepatic artery, the inflow of perfusable microvasculatures can be occluded with embolic agents loaded via a catheter. The efficacy of embolic agents is easily measured through the quantification of tumor cell death, vessel regression, cytokine release profile, and cell-surface marker identification.

"By integrating functional blood vessels into a liver cancer-on-a-chip system, we can replicate the unique vascular dynamics that drive hepatocellular carcinoma growth and response to embolic therapies, something traditional cell cultures and animal models cannot achieve," said Dr. Huu Tuan Nguyen, first author of the publication.

"This platform allows us to deliver embolic agents directly into microengineered tumor vessels, closely mimicking the clinical procedure and providing unprecedented insight into how tumors respond at the cellular and tissue level," said Dr. Vadim Jucaud. "Beyond therapy testing, the vascularized model provides a powerful tool to study how embolization alters tumor hypoxia, immune infiltration, and angiogenic signaling, all of which are critical to advancing precision oncology."

This innovative model provides insight into embolization dynamics and opens the door to next-generation embolic agents, potentially accelerating translation of discoveries into clinical treatments for liver cancer.