For the first time in the world: A scientific achievement for researchers from Tel Aviv University who were able to print a complete and active cancerous growth of the glioblastoma type in a three.dimensional printer. The printed tumor includes a bifurcated system of tubes through which blood cells and drugs can flow in a manner that mimics the true tumor.

Thanks to the breakthrough, the researchers estimate that in the future it will be possible to quickly predict the most appropriate treatment for the patient and at the same time develop new drugs at a much faster rate than what exists today.

The tumor printout is based on samples of patients taken directly from the operating rooms in the neurosurgical department at Sourasky Hospital in Tel Aviv. The results of the new study are published today in the prestigious journal Science Advances.

The study was led by Prof. Ronit Sachi.Painero of the Sackler Faculty of Medicine and the Purple School of Neuroscience, which heads the Center for Cancer Biology Research, the Cancer and Nanomedicine Laboratory, and the Maurice Kahn 3D Printing Project. At Tel Aviv University. The new technology was developed by doctoral student Lena Neufeld together with laboratory members Ilam Yeni, Noa Reisman, Yael Stillerman, Dr. Dikla Ben.Shoshan, Sabina Putzi, Dr. Galia Tiram, Dr. Anat Eldar.Bock, and others. R. Sheeran Farber.

Prof. Sci.Fainero said that “Glioblastoma is the most deadly type of cancer in the central nervous system, and it is the most malignant tumor originating in the brain. In our previous study, we first identified a protein called P.Selectin, which is secreted between glioblastoma cells “Microglia, the cells of the immune system in our brain. We found that this protein is responsible for the failure of the microglia, which instead of attacking the cancer cells, encourage the spread of this deadly cancer.“

“But we detected this protein in tumors removed in patient surgery – but not in glioblastoma cells we grew in my lab, in two dimensions on petri dishes. The reason is that cancer, like any tissue, behaves very differently on a hard plastic surface compared to its behavior when it grows in the human body. 90% “Drugs fall short of the clinical trials because they fail to replicate in humans the success achieved in the laboratory,” she added.

Demonstration to illustrate brain printing by tumor within the brain environment according to a computerized three.dimensional model (Photo: Tel Aviv University)

“It’s not just the cancer cells themselves,” explained Prof. Sci.Painero, “but also the microenvironment cells in the brain, astrocytes, microglia and blood vessels connected to a microfluidic system – that is, a system that allows substances to grow into substances such as blood cells and drugs. Each model is printed. “Inside a bioreactor we created in the lab, using a gel that we sampled and replicated from the extracellular matrix taken from the patient, thus simulating the tissue itself.“

Microscopic photograph of the cancerous growth printed at Tel Aviv University (Photo: Tel Aviv University)Microscopic photograph of the cancerous growth printed at Tel Aviv University (Photo: Tel Aviv University)

“After all, the brain does not have the same physical and mechanical properties of other organs as skin, breast or bone. Breast tissue is mainly fat, bone tissue is mainly calcium; each tissue has different properties, and these properties affect the behavior of cancer cells and their ability to respond to drugs. “Growing all types of cancer on the same plastic surface – far from simulating the clinical condition optimally,” she continued.

Having successfully printed the three.dimensional tumor, Prof. Sci.Painero and colleagues showed that with the help of the model, it would be possible to quickly and efficiently predict the most appropriate treatment for a specific patient, as opposed to cancer cells growing in petri dishes.

In addition, in collaboration with Dr. Assaf Medi’s Laboratory from the Department of Pathology at Tel Aviv University School of Medicine, we genetically sequenced the cancer cells we grew in the three.dimensional model and compared them to cancer cells grown on two.dimensional plastic and to cells we healed from patients. Dimensions were much more similar to brain cancer cells in their natural environment, “added Prof. Sci.Painero.

According to her, over time, the cancer cells that grew on plastic gradually changed until they lost all connection to the cancer cells in the patient’s brain. Finally, the third proof was by measuring the growth rate of the tumors. Glioblastoma is a violent disease in part because it is unpredictable: if the heterogeneous cancer cells are injected separately into a model, in some, the tumor will be dormant and in some, an active tumor will develop rapidly. It makes a lot of sense because we humans can die in a good return without even knowing we have had such ‘dormant’ tumors. “

“On the other hand, on the plastic plate in the lab, all the tumors grow at the same rate and spread in the same way. In the tumor we printed on the 3D printer, the tumor development rate matches the development we see in patients or model animals,” she added.

Blood vessel printed on a 3D printer (Photo: Tel Aviv University)Blood vessel printed on a 3D printer (Photo: Tel Aviv University)

According to Prof. Sci.Painero, this is an innovative approach that will also make it possible to develop new drugs as well as discover new targets for suitable drugs at a much faster rate than what exists today. Hopefully in the future, this technology will enable customized medicine for patients.

“If I take a sample from a patient’s tissue, along with its extracellular matrix, I can print out a hundred different tumors from this sample and test many drugs and combinations to find out which drug or combination of drugs is more appropriate for that specific tumor. Alternatively, development allows us to test lots. “Different compounds on a tumor printed on a three.dimensional printer, and decide in which compound it is worth investing the resources to try and develop further as a drug up to the clinical stage,” she explained.

But she says, “Perhaps the most exciting part is finding the target proteins and target genes in the cancer cells, which is very difficult to do in tumors that are in patients ‘or model animals’ brains. “Dimensions that mimic the tumor we find in patients in the best way.“

The study was funded by the Maurice Kahn Foundation, the Israel Cancer Research Foundation (ICRF), the European Research Council (ERC), the Association for the War on Cancer, the National Science Foundation and Check Point Software Technologies Ltd.

By Editor

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