A stem cell is essentially a ‘’blank’’ cell, capable of becoming another, different type of cell anywhere in the human body. Microscopic in size, stem cells are big news in medical and science circles because they can be used to replace or even heal damaged tissues and cells in the body, a sort of built-in repair system for humans.
In a first for medical science, UNC Lineberger researchers are turning skin cells into cancer-hunting stem cells that destroy brain tumors known as glioblastoma – a discovery that can offer, for the first time in more than 30 years, a new and more effective treatment for the disease.
Glioblastoma is a fast-growing, aggressive form of brain cancer. The survival rate beyond two years for a patient with a glioblastoma is only 30 percent because it is so difficult to treat. Even if a surgeon removes most of the tumor, it’s nearly impossible to get the invasive, cancerous tendrils that spread deeper into the brain, and inevitably, the remnants grow back. Most patients die within a year and a half of their diagnosis.
“Current strategy to treat the disease is surgical removal of the tumor, followed by radiation and chemotherapy in hopes of killing remaining cancer cells. All of those treatments help, but it’s a very difficult disease, and patients desperately need a better standard of care,” says Matt Ewend, MD, a UNC Lineberger member, Van L. Weatherspoon, Jr. Eminent Distinguished Professor and chair of the Department of Neurosurgery at UNC.
Researchers want to improve those statistics by developing a new personalized treatment for glioblastoma that starts with a patient’s own skin cells, with the goal of getting rid of the cancerous tendrils, effectively killing the glioblastoma.
“Long-term survivors of glioblastoma are rare. We hope to change that,” Matt Ewend, MD
Shawn Hingtgen, PhD, a UNC Lineberger member and an assistant professor of molecular pharmaceutics in the UNC Eshelman School of Pharmacy, says his team has engineered these stem cells so that they can actually hunt down the cancerous tumor cells.
“This requires a conversion process called ’direct reprogramming’,” explains Hingtgen. “We turn skin cells known as fibroblasts into special neural stem cells. Working with mice, our team has shown that these so-called ‘induced neural stem cells’ have an innate ability to move throughout the brain and home in on any remaining cancer cells. The team also showed that these stem cells could be engineered to produce a tumor-killing protein, creating a promising new strategy for killing glioblastoma cells embedded throughout the normal brain.”
In mouse studies, survival rates doubled and tripled. The hope is the new method would do the same in human patients.
“In a test dish with pink human tumor cells, scientists can see the green stem cells hunting down the tumor cells,” says Ewend. “Those cells can see things that I can’t see as a surgeon. They can find cells I can’t find and offer us a chance to get rid of those last few remaining cells that cause the recurrences.”
Researchers are already collecting biopsies from glioblastoma patients to test the concept on human tissue. They hope it will result in human trials and an effective therapy to add to current treatments. If ultimately successful in human trials, UNC researchers envision the concept being adapted to fight other types of brain cancer, including pediatric cases and ‘’breast-to-brain-cancer’’ in women.
“Our work represents the newest evolution of the stem-cell technology that won the Nobel Prize in 2012. It’s the first time this direct reprogramming technology has been used to treat cancer, and we have high hopes for success,” Hingtgen says.