3D-printed brains could shed light on brain cancer treatments

Researchers from Northeastern University (MA, USA) have 3D printed biomaterial-based models of human brains to aid medical professionals in understanding glioblastoma growth, as well as accelerate the discovery of potential treatments.

As described in Science Advances, the team has successfully 3D-printed the human brain models from an agglomeration of human brain cells and biomaterials.

This is a very difficult brain tumor to treat and it’s also difficult to do research on the brain tumor, because you cannot really see what’s happening,” explained Guohao Dai, Associate Professor of Bioengineering at Northeastern University.

Researchers are not typically able to directly observe how tumor cells grow and their response to treatments within the human brain. Often, research is conducted in animal models and requires dissection, reducing the capability for daily monitoring of the same tissue in the same living tissue.

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In an effort to be able to study glioblastoma more closely, Dai ‘grew’ a 3D model of brain tissue, ready for tumor cells to infiltrate.

We use human brain blood vessel cells, and connect them with all the neurons, pericytes, astrocytes, the major cell types in the human brain,” Dai explained. A water-based substance known as a hydrogel serves as a matrix to hold these cells in place. “Then we use 3D printing to stack them in three-dimensional fashion.”

Glioblastoma stem cells, derived from brain tumor patients, were placed in the centre of the model.

We can observe how the brain tumor cells aggressively invade, just like what we see in patients,” Dai added. “They invade everywhere.”

The team then used laser scanning to create a 3D ‘snapshot’ of the cellular structure. The combined bioprinting and imaging methodology allowed the team to evaluate the effectiveness of chemotherapy drug, temozolomide.

We treated the tumor with the same kind of drug you give to a patient when they undergo chemotherapy,” Dai added. “We monitored this chemotherapy over 2 months. And what we found was the chemotherapy was not able to kill the tumor.”

In line with the reported patient experience of patients with glioblastoma, the team observed the tumor shrink initially in response to the drugs, before aggressively growing back.

This particular chemotherapy is not effective for the brain tumor,” Dai further commented. “We need to develop and screen other chemotherapy drugs.”

The team hopes that the 3D model will be able to ‘weed out’ unsuccessful drug candidates quickly, ensuring that only the most effective therapeutics progress into animal and human trials.

You have a tremendous amount of time and cost associated with animal research. With our 3D glioblastoma model and imaging platform, you can see how the cells respond to radiation or chemotherapy very quickly,” Dai concluded.

Sources: Ozturk MS, Lee VK, Zou H, Friedel RH, Intes X, Dai G. High-resolution tomographic analysis of in vitro 3D glioblastoma tumor model under long-term drug treatment. Science Advances. 6(10), eaay7513 (2020);

Lead image: Glioblastoma stem cells aggressively invade a model made of human brain cells and biomaterials. Photo courtesy of Guohao Dai. Dai is an Associate Professor of Bioengineering in the College of Engineering at Northeastern University. Credit: Matthew Modoono/Northeastern University.

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