Many drugs make it through preclinical research with potential and promise. But in clinical trials, drugs, especially cancer therapies, often fail. That may be because cancer models are inadequate and do not reliably replicate the tumor environment.
Neuroscientist Ronit Satchi-Fainaro and her team at the University of Tel Aviv have created a 3-D-printable bioink that mimics the brain tumor microenvironment. The new model may one day replace cell culture and animal models for drug discovery, screening, and development.
“They developed a realistic model that contains tumor environmental cells and a functioning vascular network in addition to tumor cells… and showed that the model is more similar to real tumors than 2-D cell line models,” said Shai Rosenberg, a neuro-oncologist at Hadassah Medical Center, who was not involved in the new work.
Many drugs show promise in the lab, but approximately 90 percent of drugs fail clinical trials. “We wanted to dramatically increase our ability to predict if a drug will be successful in the clinic,” Satchi-Fainaro said. “Growing cancer on identical plastic surfaces is not an optimal simulation of the clinical situation.”
Satchi-Fainaro and her team aimed to recreate cancer tissue, including the microenvironment, blood vessels, and immune cells. By using 3-D bioprinting technology, the researchers could work with a wide range of biomaterials and control how multiple cell types organized in 3-D space, meaning that the model would imitate the tumor microenvironment better than other techniques such as 2-D cell culture.
They created a fully functioning 3-D model of a glioblastoma tumor, including 3-D-bioprinted cancer tissue and the surrounding tumor microenvironment that affects its development. Extracellular matrix and fluid envelop the 3-D cancer tissue, which communicates with the environment via functioning blood vessels.
Other 3-D bioprinted cancer models exist, but this is one of the first to combine tumor cells with components of the tumor microenvironment and contain functional blood vessels.
Unlike cancer cells grown in two dimensions on plastic plates, the 3-D-bioink platform mimicked growth rate, drug response, and genetic signatures of glioblastoma cells grown in mouse models, Satchi-Fainaro reported in Science Advances.
Rapidly screening drugs that will work well for each individual patient is possible. “If we take a sample from a patient’s tumor, together with surrounding tissues, we can 3-D-bioprint 100 tiny tumors and test many different drugs in various combinations to discover the optimal treatment for this specific tumor,” Satchi-Fainaro said.
Satchi-Fainaro sees the model as powerful enough to replace cell culture and animal models for robust and reproducible personalized therapy screening. Dinorah Friedmann-Morvinski, who is also a neuroscientist at the University of Tel Aviv but was not involved in the research, sees that possibility as well. “The model could really help screening for drugs where the 2-D culture system failed,” she said.
The model also has potential to unlock drug targets for glioblastoma. When a tumor is inside a patient or animal model, it is difficult to find drug targets, but “our innovations give us unprecedented access with no time limits to 3-D tumors mimicking the real thing, enabling optimal investigation,” Satchi-Fainaro said.
L. Neufeld et al., “Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment,” Science Advances, 7(34):eabi9119, 2021.