3D-Bioprinted Mini Brain helps scientist better understand the cellular interactions in brain cancer


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Glioblastoma is the most aggressive cancer that originates within the brain, formed from cells called astrocytes that support nerve cells. It is known that these formed glioblastoma cells can recruit and polarise immune cells called macrophages, which in turn, support progression and invasion of the tumor. Although it is known that interaction between glioblastoma cells and these immune cells occur,the exact crosstalk that takes place is not fully understood. To help investigate this interaction and  test therapeutics which target it, scientists of the University of Twente have utilised 3D bioprinting technology, and created a 3D printed brain model to represent the delicate tissue around the tumor.

The strategy employed by Dr Heinrich and his team, is based on a two-step bioprinting process in which they first print a larger brain structure using a bioink incorporating a macrophages cell line with an empty cavity, then in the second step this space is filled with a glioblastoma cells embedded bioink. This “mini-brain” design makes it possible to remove the tumor as a whole, and  to examine the effect on the remaining cells., meaningphenotypic alterations in both cell types resulting from their close interaction can be studied.

Compared to existing lab models, such as 2D and animal research, the new 3D model seems more effective in testing new drugs. Dr. Heinrich and his team could demonstrate that in the mini‐brain, glioblastoma cells actively recruit macrophages and polarize them into a glioblastoma-associated macrophage (GAM) specific phenotype, showing clinical relevance to transcriptomic and patient survival data. Furthermore, they demonstrated how therapeutics can inhibit the interaction between GAMs and tumor cells resulting in reduced tumor growth and greater sensitivity to chemotherapy.

“For certain tumor markers, we see that they are up to 1,000 times higher than we observe in 2D studies. This approaches realistic values far better”, says Dr Heinrich. “This clearly has an effect on medication as well. In the past, the treatment that worked well in animals and 2D-lab experiments sometimes failed in clinical trials. The 3D model shows why it isn’t working because the dosage should be much higher, for example.”

 

Source: Marcel A. Heinrich et al., Cancer Modeling: 3D‐Bioprinted Mini‐Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics, Advanced Materials, 14/2019

 

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