A new look at complex tumor cells

TROY, N.Y.—How do you turn around the situation with a disease so difficult to treat that average survival is a mere 11-15 months after diagnosis? While not the only disease with this kind of distinction, for glioblastoma—which is the most common primary malignant brain tumor, as well as the most aggressive cancer that begins in the brain—the answer here is the usual answer: Better understanding of disease etiology and progression leads to better treatments, faster.

Early March saw research published in Science Advances by Dr. Xavier Intes, a professor of biomedical engineering at Rensselaer Polytechnic University, and colleagues that supports that better understanding with a novel imaging technique and 3D printing.

More specifically, Intes joined with a multidisciplinary team that included researchers at Northeastern University and the Icahn School of Medicine at Mount Sinai to demonstrate a methodology that combines the bioprinting and imaging of glioblastoma cells in a cost-effective way that more closely models what happens inside the human body.

“There is a need to understand the biology and the complexity of the glioblastoma,” said Intes, who is also the co-director of the Center for Modeling, Simulation and Imaging for Medicine (CeMSIM) at Rensselaer. “What’s known is that glioblastomas are very complex in terms of their makeup, and this can differ from patient to patient.”

The creation of the model was led by Dr. Guohao Dai, an associate professor of bioengineering at Northeastern University, with the team making bioinks out of patient-derived tumor cells and printed them along with blood vessels to create the 3D tumor cell model. According to the researchers, the vasculature that they created allowed the printed tissue to live and mature so that researchers could study it over a matter of months.

As noted by Rensselaer in a news release about the work, “The bioprinted blood vessels also provided channels for therapeutics to travel through—in this case, the chemotherapy drug temozolomide. In the body, drug delivery to glioblastoma cells is especially complicated because of the blood-brain barrier, a wall of cells that blocks most substances from reaching the brain.”

But because their 3D model reportedly could more closely replicate this impediment, the team’s method allowed for a more accurate evaluation of drug effectiveness than by directly injecting the drug into cells.

“That’s the unique part of the bioprinting that has been very powerful,” Intes commented. “It’s closer to what would happen in vivo.”

But it wasn’t just about the model itself; the other part of the equation was how to view the model and what was happening. To that end—to see if the drug was making it to the glioblastoma cells and working—Intes and his team developed a specialized technique that could quickly take images of the bioprinted tissue at the cellular level through the thick Plexiglas container in which the tissue was contained. Notably, it had to do so using as little light as possible, so as to not damage the cells.

“We developed a new technology that allows us to go deeper than florescence microscopy,” Intes explained. “It allows us to see, first, if the cells are growing, and then, if they respond to the drug.”

This technique, according to Intes, could allow researchers to evaluate the effectiveness of multiple drugs at the same time. However, it is not yet realistic for studying the effectiveness of certain therapeutics on a person’s individual tumor, he points out, because of the short time period in which clinicians often have to provide treatment.