‘A Big Step’: UNC Researchers Use Stem Cells to Treat Brain Cancer

University of North Carolina researchers have made recent breakthroughstoward a treatment for a common and aggressive type of brain cancer using human cells.

In less than a year, researchers at UNC have made several advancements in the treatment of glioblastoma, and their work was published in the Feb. 1 issue of Science Translational Medicine. The research describes how human stem cells made from human skin cells can hunt down and kill brain cancer.

Last year, the UNC team led by Shawn Hingtgen, an assistant professor in the Eshelman School of Pharmacy and member of the Lineberger Comprehensive Cancer Center, used the technology to convert mouse skin cells to stem cells that could home in on and kill human brain cancer. The treatments increased time of survival 160 to 220 percent, depending on the tumor type, according to a news release from the university Thursday.

Now the team has shown not only that the technique works with human cells, but that it works quickly enough to help brain cancer patients whose median survival rate is less than 18 months and chance of surviving longer than two years is 30 percent.

“Speed is essential,” Hingtgen said. “It used to take weeks to convert human skin cells to stem cells. But brain cancer patients don’t have weeks and months to wait for us to generate these therapies. The new process we developed to create these stem cells is fast enough and simple enough to be used to treat a patient.”

The standard care for glioblastoma are surgery, radiation and chemotherapy, and that hasn’t changed in 30 years. Within months, the tumor returns in almost every single patient, invariably sending tiny tendrils out into the surrounding brain tissue. Drugs can’t reach them, and surgeons can’t see them, so it’s almost impossible to remove all of the cancer, said Ryan Miller, a coauthor of the study and a neuropathologist at UNC Hospitals and associate professor at the UNC School of Medicine.

“We desperately need something better,” said Hingtgen.

The UNC team’s research relies on “skin flipping,” a technology for creating neural stem cells from skin cells that won a Nobel Prize in 2012. Researchers harvest fibroblasts – the skin cells responsible for producing collagen and connective tissue – from the patient and reprogram those cells to become what are called “induced neural stem cells,” which have an innate ability to home in on cancer cells in the brain.

But those stem cells still aren’t enough. On their own, the stem cells can only track down the tumor and then bump against it – not kill it. So the team had to engineer stem cells that could carry therapeutic agents that the cells can launch at the tumor to kill it.

The therapeutic agents that the UNC team’s cells carry is a protein that activates an inert substance called a “prodrug” that is given to the patient. The cells can then generate a small halo of drug that is located just around the stem cell rather than it being circulated through the patient’s body, which reduces unwanted side effects.

“We’re one to two years away from clinical trials, but for the first time, we showed that our strategy for treating glioblastoma works with human stem cells and human cancers,” said Hingtgen. “This is a big step toward a real treatment – and making a real difference.”