Researchers at the University of Michigan in Ann Arbor have developed a 3-D structure for growing cell cultures that could enable doctors to test medications on model tumors from patients’ own cells.
Unlike previous devices, the new structure is made from protein fibers that cells know how to modify.
“We can potentially use the cultures to do things like drug testing or single cell analysis, which may help us identify the best treatments for a patient’s cancer,” says Gary Luker, professor of radiology.
Some patients can have samples of their cancer cells grown in mice for drug testing and analysis, but the cancer cells don’t always grow, and the process takes months, Luker says. The scaffold, which is essentially an advanced petri dish, could enable doctors to get answers about the effectiveness of drugs in days or weeks.
Earlier scaffolds that tried to mimic the structure and composition of the gel-like network that binds a collection of cells into a tissue, also have mixed records.
“Rather than trying to guess at what the tumor cells’ microenvironment ought to be, we’ve made a space where they can create their own cell niche, as they do in the body,” says Stacy Jordahl, a recent chemical engineering Ph.D. graduate from U-M and first author on the paper in Advanced Materials.
The team created a network of fibronectin, a protein that attaches cells to the connective gel. Cells in tissues stretch out the fibronectin, but the substance coils up if not held open. The new method produces a coating of stretched-out fibronectin without having to pull or hold it open.
Engineers built a grid of microscale cubicles, each half a millimeter to a side. Then, they repeatedly poured a solution containing fibronectin over the surface. The tug of the moving liquid was enough to draw the fibronectin out into networks of fibers that interlaced across the structure.
“With this engineered way to draw proteins into a network of fibers, we can produce a more natural environment for growing cancer cell cultures that enable us to test drugs or understand cancer biology,” says Joerg Lahann, the Wolfgang Pauli collegiate professor of chemical engineering and director of the Biointerfaces Institute.
Cancer researchers then used the structures to culture cells that had been removed from breast cancer patients.
“There have been a lot of technologies and approaches devised to try to grow cancer cells in culture that haven’t worked so well. Most cancer cells die out when cultured in artificial conditions,” Luker says. “In this system, we could pretty consistently grow out the cultures at least for short periods of time.”
The cells also changed as they grew on the network, becoming more like the kind of cells that are believed to spread cancer to other parts of the body. These cells are the most imperative to kill.
The work was funded by the National Cancer Institute, the National Science Foundation, the Department of Defense, and the National Institutes of Health.
