Device to Study Bone-Seeking Breast Cancer Wins Army Idea Award

Newswise — A tool that allows biologists to study bone-seeking breast cancer cells has been developed by materials researchers at Penn State University. The device, called a compartmentalized bioreactor, has been shown to keep bone cells alive and healthy indefinitely, according to Erwin Vogler and graduate student Ravi Dhurjati, the inventors. Together with Penn State biologists Carol Gay and Andrea Mastro, the team, which includes graduate student Laurie Shuman, recently won a highly competitive Army Idea Award to study pernicious bone-seeking breast cancer using the bioreactor.

"In conventional cell culture, bone cells only survive a few weeks to 30 days, not long enough to develop a cell matrix complex enough for study. Because waste products must be removed and nutrients replaced, the cells go from feast to famine, feast to famine every few days between refeeding," says Vogler, associate professor of materials science & engineering and bioengineering. This contributes to "culture shock," the strain that cells experience when they are removed from the body. "In the bioreactor, you don't have to perturb the cells with medium exchange. In fact, we refresh the bioreactor with growth medium only every 30 days instead of every 3 days, as is traditionally done."

The bioreactor uses gas permeable polymer films in a stainless steel compartmentalized culture chamber small enough to be held in one hand. Bone cells called osteoblasts are placed into an enclosed-dish growth space separated from the medium reservoir by a dialysis membrane. As cells grow and use up nutrient, more nutrient dialyzes in from the medium reservoir. As waste builds up it dialyzes out, based on concentration levels. Samples are removed through "taper ports" without disturbing the growth space. The principle, called "simultaneous growth and dialysis," was invented by G.G. Rose in the 1960s and then largely forgotten, according to Vogler.

"What makes the difference between a bioreactor and a culture dish is that the osteoblasts are more robust," says Dr. Gay, professor of biology and an expert in breast cancer cells. "You can see that they have a cuboidal shape and they are making lots of protein. In contrast, the dish culture cells are flat and make little protein."

Inside the body, bone cells grow in layers and form a community of cells that interact. In the culture dish, on the other hand, cells remain in a monolayer with little interaction. In the bioreactor, cells are currently growing in a matrix of tissue six to eight cells deep, previously unreported in vitro. They are, according to Mastro and Gay, "approaching the appearance of normal bone cells in the body."

The group is now adding breast cancer cells to grad student Ravi Dhurjati's bone cell cultures in order to test cancer drugs. Using a confocal microscope to study layers of bone matrix, the biologists have observed metastasis and tumor formation, important hallmarks of cancer that have never been observed in the lab.

"We have reached six months in culture, which was unheard of. We are looking for one year, which is absolutely unheard of. Now you can actually see chips of bone," says Vogler. "We will be able to study osteogenesis and osteopathology in an environment that better simulates conditions inside the body. Then we can go on to other degenerative bone diseases, and then to other kinds of cells " maybe we can even grow brain cells."

More information on the bioreactor is available on the Materials Research Institute website at www.mri.psu.edu. Click on the Research Spotlight. Funding for this research was provided by Penn State's Materials Research Institute and Huck Institutes of the Life Sciences, and by the Pennsylvania Department of Health through the Tobacco Settlement Formula Fund. The Materials Research Institute supports important discoveries in materials science and cross-disciplinary research at Penn State University.