Clinical researchers are constantly thwarted by the inability to quickly and easily try new therapies in tumors and other disease targets. Tumors within the brain are particularly hard to study because of the difficulty with access and the incredible fragility of nearby tissues. Researchers at Tufts University have just developed a way to create an environment that closely mimics that of the brain and were able to grow pediatric and adult tumors within it. The microenvironment allows for non-invasive imaging of the tumors and for easy manipulation of the cells growing within.
The model tumors were grown in the presence of brain-derived extracellular matrix (ECM), a 3D network of collagen, proteins, and other large molecules that supports brain tissue and helps to guide cellular growth. This is important, since there’s evidence pointing to the ECM being involved in tumor growth and the feedback loop that changes genetic and protein expression within tumor cells.
“The power of this platform is that we can tune the composition of the ECM to find out the role of each component in tumor growth, and we can see the effect on tumor cells derived directly from the patient,” said David Kaplan, the lead researcher on the study appearing in Nature Communications. “Another important feature is that we can track the 3D growth of cells with non-invasive two-photon excited fluorescence metabolic imaging via the contributions of Irene Georgakoudi’s team on the project. In other words, we can use non-invasive imaging to assess if they are viable and growing, or stressed and dying, in real-time.”
The team grew ependymoma tumors, a pediatric brain cancer, as well as glioblastoma tumors, which occurs in adults, within the matrix that they developed. They can even take cells from a primary tumor in a patient and transfer them to their platform, allowing them to grow and study how the ECM affects tumor growth and development. Flat petri dishes and 3D environments without an ECM were previously the only available options, and tumor growth within such environments was probably not very natural compared with that in a more realistic environment.
“With this platform, we have the potential to better understand what dictates the invasive behavior of brain tumors and screen drugs for their effect on the tumor growth of patient-derived cells,” said Disha Sood, graduate student in Kaplan’s lab and first author on the study. “Although it’s a preliminary notion, the ability to maintain viable cultures of patient-derived tumor cells and metabolically track them non-invasively, suggests the possibility of monitoring the cells’ behavior and drug sensitivity over time, to inform treatment decisions.”
Study in Nature Communications: 3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors