Human Stem Cells Repair Radiation Damage in Rat Brains

Radiation is a powerful treatment for brain cancer, but this potentially life-saving treatment comes with a heavy cost, which is permanent damage to the brain.

Preclinical work at Memorial Sloan Kettering Cancer Center has shown that human stem cells can be used to make cells that repair radiation-induced damage in the brain.

When rats were treated with radiation and then given cocktails to the human stem cells, they regained the cognitive and motor functions that were lost after brain irradiation.

In the brain, stem cells called OPCs or oligodendrocyte progenitor cells mature into oligodendrocytes that produce the protective myelin coating that surrounds axons in the central nervous system. During radiation treatment, OPCs die off and are depleted. Because OPCs help shield and repair the myelin sheath throughout the life of the organism, depletion of them threatens the integrity of the myelin sheath, which threatens the proper transmission of neural impulses throughout the brain.

A research project led by neurosurgeon Viviane Tabar and her research associate Jinghua Piao wanted to use stem cells to replace these lost OPCs. They used human embryonic stem cells and human induced pluripotent stem cells to make cultured OPCs.

In the next phase of the experiment, Taba, Piao and their coworkers treated rats whose brains had been irradiated with their cultured OPCs. After injection of the stem cell-derived OPCs, brain repair was evident and the rats regained their cognitive and motor function that they had previously lost as a consequence of radiation exposure.

The treatment appeared quite safe since none of the animals developed any tumors or aberrant growths.

The ability to repair radiation damage could mean that the quality of cancer survivors could be greatly improved and it could also expand the therapeutic window of radiation, according to Tabor.

“This will have to be proven further, but if we can repair the brain effectively, we could be bolder with our radiation dosing, within limits,” said Tabor.

Such a treatment scheme could also be very important in children, for whom physicians must use lower doses of radiation to limit brain damage.

Rapamycin Prevents Side Effects Of Radiation Therapy By Protecting Stem Cells

Radiation therapy is very heavily used to treat many different types of cancer. Unfortunately, radiation damages normal cells and tissues and can have horrible side effects that debilitate patients. However, a class of drugs known as inhibitors of mTOR, which stands for mammalian target of rapamycin, can prevent the tissue damage normally caused by radiation. These drugs protect against radiation-induced damage by protecting normal stem cells. Since these stem cells help repair the damaged tissues, these drugs speed recovery and improve outcomes. These results come from a preclinical study published in the September issue of the journal Cell Stem Cell.

The senior author of this study, J. Silvio Gutking of the National Institute of Dental and Craniofacial Research, made this comment about his study: “We can exploit the emerging findings for the development of new preventive strategies and more effective treatment option for patients suffering this devastating disease.”

After undergoing radiation therapy, cancer patients often suffer from a painful condition called mucositis. Mucositis is characterized by the swelling of tissues in the mouth, and this swelling can prevent patients from drinking and the pain of this condition drives them to heavily rely on narcotic pain killers. Mucositis and other types of radiation-induced tissue damage are induced by depletion of stem cells capable of repairing damaged tissue.

In their study, Gutkind and his team discovered that an mTOR inhibitor called rapamycin protects stem cells extracted from the mouths of healthy individuals against radiation-induced damage. Fortuitously, rapamycin does not convey the same protections to cancer cells. The drug extended the lifespans of normal stem cells and allowed them to grow after irradiation. Rapamycin exerted its protective effects by preventing the accumulation of harmful molecules called reactive oxygen species (ROS). Also mice that received rapamycin during radiation treatment did not develop mucositis.

Rapamycin is already approved by the Food and Drug Administration and is currently under investigation in clinical trials as a cancer prevention agent and a potential treatment of various kinds of cancer. These novel findings could have immediate and important implications for a many different cancer patients.

According to Gutkind: “Mucositis prevention would have a remarkable impact on the quality of life and recovery of cancer patients and at the same time would reduce the cost of treatment. Our study provides the basis for further testing in humans, and we hope that these findings can be translated rapidly into the clinic.”