Researchers at Kyoto University in Japan have developed a tumor-on-a-chip device that incorporates perfusable blood vessels to more accurately mimic real tumors that occur in the body. The researchers hope that the device will allow for more realistic and accurate testing of anti-cancer drugs in the lab, and have already shown that the flow of nutrients through the device can significantly affect the anti-tumor efficacy of tested drugs.
methods to test drugs have a long list of widely acknowledged drawbacks,
spurring researchers to develop an array of new technologies. “Potential
compounds are tested using animal models and cells cultured in a dish. However,
those results frequently do not transfer over to human biology,” explains Yuji
Nashimoto, a researcher involved in the study. “Furthermore, cells on a dish
lack three-dimensional structure and blood vessels. So, we came up with a plan
to construct a device that solves these issues.”
device is a tumor-on-a-chip, where tumor cells can be cultured and exposed to compounds
that have potential as anti-cancer drugs. However, the system aims to be more realistic
than many comparable devices by incorporating perfusable blood vessels through
which nutrients and drugs can be delivered to a central “tumor”.
device is approximately the size of a coin, and incorporates a central well,
where tumor cells are grown, and tiny surrounding “microposts” where vascular
cells are grown, mimicking a central tumor and surrounding vasculature.
vasculature’ allows us to administer nutrients and drugs into the system to
mimic the environment in the body,” said Nashimoto. “This allows us to have a
clearer picture of the effectiveness of cancer treating compounds.”
So far, the researchers have shown that their perfusable chip does indeed affect the results of anti-cancer drug screens, potentially more accurately mimicking the situation in the body of a human patient. Perfusing the chip with a nutrient-rich medium helped to enhance tumor cell viability and reduced the effectiveness of an anti-tumor compound at low doses, compared with a chip in which no perfusion occurred. However, at higher doses, perfusion significantly enhanced the effectiveness of the compound in killing cancer cells, demonstrating the complex relationship between blood flow and drug efficacy in the tumor environment.
“We hypothesize that at low doses the benefit of the nutrient flow outweighs the effect of the anti-tumor drug. It proves the importance of blood flow in the vasculature when screening for drugs,” said Ryuji Yokokawa, another researcher involved in the study. “Due to its size and utility, we hope the new device can expedite the tests on the countless number of potential new drugs. While many questions remain, we are happy to have developed this device and have shown that three-dimensional perfused cell culture is vital for the next step in drug discovery.”
Here’s a video from Kyoto University of green fluorescence passing through a vascularized 3D tumor culture: