Israeli ‘scientific breakthrough’ in the battle against the most dangerous type of brain cancer

Using a 3D printer, Tel Aviv University (TAU) researchers have produced a complete active and viable brain tumor with a complex system of blood vessel-like tubes through which blood cells and drugs can flow. This simulation of a real tumor of the most deadly type was described as a breakthrough by Prof. Ronit Satchi-Fainaro of the Sackler Faculty of Medicine and Sagol School of Neuroscience and director of the Cancer Biology Research Center who led the study. 


The 3D-bioprinted models are based on samples from patients, taken directly from operating rooms at the Tel Aviv Sourasky Medical Center. The new study’s results were published today in the prestigious journal Science Advances under the title “Micro-engineered perfusable 3D-bioprinted glioblastoma model for in-vivo 2 mimicry of tumor microenvironment.”


Many drugs show promising results in laboratory research, but eventually fail in clinical trials. “We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stromal cell interactions, which are essential for tumor progression,” the team said. Working with the head of the Cancer Research and Nanomedicine Laboratory and the director of TAU’s 3D-BioPrinting for Cancer Research Initiative, the new technology was developed by doctoral student Lena Neufeld winner of the prestigious Dan David Fellowship) together with other researchers at Satchi-Fainaro’s lab including Eilam Yeini, Noa Reisman, Yael Shtilerman, Dr. Dikla Ben-Shushan, Sabina Pozzi, Dr. Galia Tiram, Dr. Anat Eldar-Boock and Dr. Shiran Farber.  


“Glioblastoma is the most lethal cancer of the central nervous system, accounting for most brain malignancies,” said Satchi-Fainaro. “In a previous study, we identified a protein called P-Selectin, produced when glioblastoma cancer cells encounter microglia – cells of the brain’s immune system. We found that this protein is responsible for a failure in the microglia, causing them to support rather than attack the deadly cancer cells, helping the cancer spread.”


However, she continued, “we identified the protein in tumors removed during surgery, but not in glioblastoma cells grown on 2D plastic petri dishes in our lab. The reason is that cancer, like all tissues, behaves very differently on a plastic surface than it does in the human body. About 90% of all experimental drugs fail at the clinical stage because the success achieved in the lab is not reproduced in patients.”


To deal with this problem, the research team created the first 3D-bioprinted model of a glioblastoma tumor, which includes 3D cancer tissue surrounded by extracellular matrix that communicates with its microenvironment via functional blood vessels.


“It’s not only the cancer cells,” explained Satchi-Fainaro. “It’s also the cells of the microenvironment in the brain – the astrocytes, microglia and blood vessels connected to a microfluidic system – a system that enables us to deliver substances like blood cells and drugs to the tumor replica. Each model is printed in a bioreactor we have designed in the lab, using a hydrogel sampled and reproduced from the extracellular matrix taken from the patient, thereby simulating the tissue itself.”


The physical and mechanical properties of the brain are different from those of other organs like the skin, breast or bone. Breast tissue consists mostly of fat, bone tissue is mostly calcium; each tissue has its own properties, which affect the behavior of cancer cells and how they respond to medications. Growing all types of cancer on identical plastic surfaces is not an optimal simulation of the clinical setting, she continued. 


After successfully printing the 3D tumor, the team showed that unlike cancer cells growing on petri dishes, the 3D-bioprinted model has the potential to be effective for rapid, robust and reproducible prediction of the most suitable treatment for a specific patient. 


“We proved that our 3D model is better suited for prediction of treatment efficacy, target discovery and drug development in three different ways. The innovative approach, they said, will make it possible to develop new drugs and discover new drug targets at a much faster rate than today. They hope that in the future, this technology will facilitate personalized medicine for patients.


“If we take a sample from a patient’s tissue, together with its extracellular matrix, we can 3D-bioprint from this sample 100 tiny tumors and test many different drugs in various combinations to discover the optimal treatment for this specific tumor. Alternately, we can test numerous compounds on a 3D-bioprinted tumor and decide which is most promising for further development and investment as a potential drug. But perhaps the most exciting aspect is finding novel druggable target proteins and genes in cancer cells – a very difficult task when the tumor is inside the brain of a human patient or model animal. Our innovation gives us unprecedented access, with no time limits, to 3D tumors mimicking better the clinical scenario, enabling optimal investigation,” she concluded. 



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