Researchers 3D-Bioprint Perfusable Glioblastoma Multiforme

Delivering a glioblastoma multiforme diagnosis to a patient and their loved ones can be extraordinarily difficult, given that the median overall GBM survival rate is only around 15 months. What’s more, only 15% of patients are believed to survive five years post-diagnosis, according to the National Cancer Institute. While the current standard of care involves surgery, radiation and drug therapies, researchers are focused on finding new treatment options to improve glioblastoma survival rates.

Yet a high percentage of experimental drugs fail before they even reach clinical trials, as some hypothesize that initial pre-clinical models can be poor predictors of human efficacy. Now, however, researchers have created what they say is the first ever “perfusable 3D-bioprinted engineered” glioblastoma multiforme that they believe can serve as a platform for reproducible drug testing, which could revolutionize the way that brain cancer treatments are currently being tested.

A Breakthrough for Glioblastoma Survival Rates?

While there have been other 3D-bioprinted models of glioblastoma, they lack “the whole plethora of stromal cells and functional blood vessels, which are critical for the development and progression of the disease and evaluation of the response to the therapy,” according the researchers at Tel Aviv University who created the most recent model.

Their model attempts to better recreate the structural and vascular properties of glioblastomas as well as the environment in which they grow. “We recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia,” they write. They also created perfusable blood vessels using a sacrificial bioink coated with brain pericytes and endothelial cells.

The idea is that this 3D-printed glioblastoma model uses cancer tissue surrounded by an extracellular matrix that can communicate with its microenvironment via functional blood vessels. The model itself is based on cell samples taken directly from patients.

“Our innovation gives us unprecedented access, with no time limits, to 3D tumors mimicking the clinical scenario, enabling optimal investigation,” Dr. Satchi-Fainaro, director of the Cancer Biology Research Center at Tel Aviv University told Science Daily.

The study, published in Science Advances, examined the ability of 3D-printed glioblastoma multiforme and stromal cells to mimic that of a tumor’s natural environment. Researchers observed their model’s ability to grow, invade healthy tissue and respond to drug therapies in comparison to a live tumor. They found that their 3D model was able to mimic the actions of a live glioblastoma multiforme better than that of 2D models typically used.

Through additional testing, researchers also noticed that their 3D-printed model had a greater genetic resemblance to patients’ live cancer cells than 2D plastic-grown cells did, and the growth patterns of the 3D-printed cells mimicked that of humans and animals, as opposed to lab-grown cells which all grow at the same rate.

This gave researchers further insight into why potentially effective drug therapies may never make it to clinical trials—because drugs that may fail in a lab may perform tremendously within the human body, and vice versa. But their 3D model may be able to overcome this discrepancy, which could open new doors to not only specialized drug therapies but personalized patient care in the future.

Other Innovations in Glioblastoma Treatment

Prior to this functional 3D model, one of the greatest leaps in innovation in glioblastoma treatment came in 2005 with Stupp et al.’s landmark study of temozolomide (TMZ). Their study found that the addition of TMZ to adjuvant radiotherapy significantly improved survival rates in glioblastoma patients while remaining minimally toxic. It quickly became considered part of the standard of care for treating glioblastoma patients.

Then, in 2014, bevacizumab was added to this treatment method in the hopes of further improving survival rates. However, in a phase 3 trial, researchers found that the addition of bevacizumab did not improve survival rates. While it was later approved for the treatment of recurrent glioblastoma multiforme in 2017, its use in newly diagnosed glioblastoma patients is still under debate.

However, in 2015, tumor-treating fields (TTF) were being tested in addition to the standard of care. Researchers found that TTF significantly improved overall survival rates among glioblastoma patients. However, overall survival rates for glioblastoma patients still remain relatively poor.

One theory is that while TMZ and radiotherapy are still being considered part of the current standard of care, research has shown that the overall efficacy has declined throughout the years. It is now believed that over 50% of glioblastoma patients treated with TMZ do not respond to it.