Not all cancers are created equal. While some are easy to study in the Petri dish, others don’t do well in vitro. They often will not grow without a supporting framework of angiogenic blood vessels that supply their high metabolism with nutrients and oxygen. Performing experiments on tumors such as glioma is a difficult proposition because they only wish to reside in the body and normally don’t survive when grown outside in a laboratory environment.
Researchers at Brown University have now managed to grow a three-dimensional glioma tumor, including the supporting proximal blood vessels, and are already using it to perform experiments testing a nanomedicine approach to tumor destruction.
From the announcement:
In a series of experiments, the team showed that iron-oxide nanoparticles ferrying the chemical tumstatin penetrated the blood vessels that sustain the tumor with oxygen and nutrients. The iron-oxide nanoparticles are important, because they are readily taken up by endothelial cells and can be tracked by magnetic resonance imaging.
Previous experiments have shown that tumstatin was effective at blocking endothelial cell growth in gliomas. The tests by the Brown researchers took it to another level by confirming, in a 3-D, living environment, the iron-oxide nanoparticles’ ability to reach blood vessels surrounding a glioma as well as tumstatin’s ability to penetrate endothelial cells.
“The 3-D glioma model that we have developed offers a facile process to test diffusion and penetration into a glioma that is covered by a blood vessel-like coating of endothelial cells,” said Don Ho, a graduate student in the lab of chemistry professor Shouheng Sun and the lead author of the paper in the journal Theranostics. “This assay would save time and money, while reducing tests in living organisms, to examine an agent’s 3-D characteristics such as the ability for targeting and diffusion.”
The tissue model concept comes from Jeffrey Morgan, a bioengineer at Brown and a corresponding author on the paper. Building on that work, Ho and others created an agarose hydrogel mold in which rat RG2-cell gliomas roughly 200 microns in diameter formed. The team used endothelial cells derived from cow respiratory vessels, which congregated around the tumor and created the blood vessel architecture. The advantage of a 3-D model rather than Petri-dish-type analyses is that the endothelial cells attach to the tumor, rather than being separated from the substrate. This means the researchers can study their formation and growth, as well as the action of anti-therapeutic agents, just as they would in a living organism.
Press release: Researchers make living model of brain tumor
Abstract in Theranostics: Penetration of Endothelial Cell Coated Multicellular Tumor Spheroids by Iron Oxide Nanoparticles