Stem Cells Help Irradiated Mice Grow New Brain Cells

Radiation treatment for brain cancer can be lifesaving, but it can come at a terrible cost. The radiation that kills cancer cells also kills brain cells, destroying memories, impairing intelligence, and causing confusion.

Charles Limoli and colleagues at the University of California, Irvine, have shown that stem cells could help reverse some of this damage. In a new paper in the journal Cancer Research, Limoli shows that it’s possible to cause new brain cells to grow by injecting human neural stem cells into the brains of mice whose cognitive abilities had been damaged by radiation. The mice regained lost skills after the stem-cell treatment.

Stem cells have long been used to repair the damage caused by cancer treatment. Bone-marrow transplants for leukemia rely on stem cells to replenish blood cells, for instance. But Limoli says his team is the only one using neural stem cells to treat symptoms in the brain.

Several peers praised his work, calling it an important proof of the idea that human stem cells can repair neuronal damage.

“The results are very promising,” says Howard B. Lieberman, professor of radiation oncology and environmental health sciences at Columbia University. “If the findings continue to be as positive as what’s published in this paper, I would assume Dr. Limoli will take great effort to try to move it into the clinic as quickly as possible.”

Limoli’s team irradiated three groups of mice, later treating two of them with human neural stem cells. The third, a control group, received a sham surgery, but no cells were implanted. One month after the damage, 23 percent of implanted stem cells were active in the brains of the first group of mice. After four months, 12 percent were still active in the second group. Using cellular labeling, Limoli’s team also showed that tens of thousands of new neurons and astrocyte cells had grown in the brains of the treated mice. The treated mice performed better than the untreated ones on cognitive tests, and recovered their preradiation abilities.

Protein activity in the treated mice suggests that the implanted stem cells are integrating into the brain, Limoli says, replacing cells that have been lost or damaged.

Both Limoli and Lieberman say the treatment could also be effective against “chemo brain,” a side effect often reported by breast cancer patients. The chemotherapy can impair their ability to focus and think clearly.

Rob Coppes, a radiation and stem-cell biologist at the University Medical Center Groningen, in the Netherlands, says he would next like to see Limoli test how long the benefits of the stem cells last. He also hopes Limoli will repeat his experiments using induced pluripotent stem cells (iPS cells), adult stem cells that have been converted back to an embryonic-like state. These would likely be the cells that doctors would use in patients. Ideally they’d be taken from the patients themselves to avoid an immune rejection.

It will be important to show that mice—and later, humans in a trial—don’t reject these cells, and also that the stem cells don’t trigger new cancers, says Coppes, who employs stem cells in his own work, which involves regenerating salivary glands.

Limoli plans to carry out further work involving human neuronal stem cells and iPS cells. He also wants to figure out the optimal time to transplant these stem cells into the brain.