Can Stem Cells Be Taught to Repair a Radiation-Damaged Brain?

By Eva Kiesler,

Friday, February 6, 2015

Fibrous extensions of a nerve cell (red) and an oligodendrocyte (green) growing on top of the nerve cell
Summary

In a recent study, Memorial Sloan Kettering scientists used stem-cell engineering to repair brain injuries in rats. The results raise hope for future therapies that could fix nerve damage in cancer patients who need brain radiation.

Here at Memorial Sloan Kettering and elsewhere, scientists are cultivating the art and science of manipulating embryonic stem cells — the immature cells from which all the body’s organs and tissues develop — to form nerve cells, muscle cells, insulin-producing cells, and essentially any cell type of interest.

Our investigators have used stem-cell engineering to create nerve cells that might be used to treat Parkinson’s, and have also developed advanced tools for research into melanoma, pancreatic cancer, a rare brain tumor, and other diseases.

Today, in an article published in the journal Cell Stem Cell, an MSK research team reports on another potential use of the technology: as a way to heal radiation-induced brain injury.

“Some cancer patients who receive radiation to the brain eventually experience cognitive problems, such as learning or thought-processing difficulties, or reduced motor skills,” says stem-cell scientist and neurosurgeon Vivian Tabar, who led the study. “And often the damage is permanent.”

As patients live longer, quality-of-life issues are becoming more obvious.
Viviane Tabar MSK stem-cell scientist and neurosurgeon

She adds that there’s a growing need to find ways to alleviate these complications. “As we get better at treating some cancers and our patients live longer, it’s becoming increasingly obvious that many of them suffer from long-term quality-of-life issues.”

The researchers turned stem cells into young central nervous system cells that can mature into oligodendrocytes, which support nerve cells. After exposing rats to brain radiation, they transplanted the engineered oligodendrocytes into the animals’ brains. The cells repaired some of the radiation injury and helped the animals recover a number of brain functions that had been compromised by the treatment.

The Late Side Effects of Brain Radiation

Radiation to the brain is used to treat primary or metastatic brain tumors as well as to prevent the spread of small cell lung cancer or leukemia to the brain. The treatment can be very effective in terms of managing the cancer, but for some patients, it impairs long-term quality of life, even when done with cutting-edge methods such as stereotactic radiosurgery.

The severity and types of complications vary depending on the amount of radiation and other therapies used, as well as the patient’s age. “For example,” Dr. Tabar explains, “learning difficulties are more serious in children and may lessen their chance of achieving higher education or maintaining a job in the future.”

The problems often don’t show up until months or years after cancer treatment has ended, and their underlying causes are complex.

Back to top

Rats in a Box

In the study, the researchers focused on one of the best-understood mechanisms of radiation-induced brain damage: the loss of oligodendrocytes. These cells produce a substance called myelin, which forms a supple casing around nerve fibers. Like the plastic coating around an electric copper wire, the myelin sheath insulates nerve cells and allows them to transmit their signals very quickly.

In people whose oligodendrocytes have been depleted by radiation, some brain functions may weaken as myelin production drops and nerves are insufficiently coated.

myelin-coated nerves

The researchers devised a technique to generate oligodendrocytes from human embryonic stem cells in the large amounts needed for transplantation. They also developed a rat model to study the neurological side effects of radiation to the brain. “We gave the rats repeated doses of radiation and showed that they developed complications similar to those seen in cancer patients,” explains postdoctoral fellow Jinghua Piao, the first author of the study.

For example, in one of the experiments she used to test cognition, Dr. Piao put the rats in a box together with a few items. After some time, she introduced a new item into the box and observed the rats’ behavior. Compared with a control group, those rats that had received radiation were less capable of distinguishing the new item from the more-familiar ones.

Back to top

Hope for Clinical Translation

Next, the researchers transplanted the engineered oligodendrocytes into the brains of these rats. “The cells were able to spread across most of the brain, integrate into the tissue, and add myelin to the nerves,” Dr. Piao says.

“And not only did the grafted oligodendrocytes repair the physical damage,” Dr. Tabar adds, “they also helped the rats improve a number of brain functions such as learning, memory, and balance.”

The findings suggest the technology might be safe if used as therapy. “No animals developed tumors or other complications as a result of the transplant, and the cells appeared to behave like natural oligodendrocytes,” she says, adding that a lot of work remains before the method can be tested safely in patients.

If the research eventually makes it into the clinic, it could offer promising treatment strategies. Stem cell–derived oligodendrocytes could potentially be given to patients who undergo brain radiation to alleviate damage. The approach could improve patients’ quality of life and also extend the use of radiation to some patients for whom the potentially curable treatment is presently too risky.

“Sometimes brain radiation can’t be used, especially in children, because the side effects are so damaging,” Dr. Tabar explains. “But with a way to fix the problem, the risks could become more manageable.”

Read more about the research in Science News.

Back to top

This research was supported by the New York State Stem Cell Board (NYSTEM) and by the National Institute of Neurological Disorders and Stroke under grant number R01NS054009.

Comments

Good job Doc. Thumbs up

Some important questions that still have to be answered are if adults engineered stem cells can act as cellular therapeutic methods of regeneration
New emerging cold atmospheric plasma technology may serve as replacement for chemotherapy or reduced doses and cold plasma itself may induce the reverberation and growth of damages tissues. An emerging field of science and technology.

Wow,

Very impressive article. Also very scary. Our Mom had small cell lung cancer in 2/87 and was treated elsewhere. She had radiation to the brain as part of her treatment protocol at the end of the treatment period. She 67 at the time. A few years later, she started exhibited short term memory problems. She went on to get worse and worse. She had a preliminary diagnosis of Alzheimer's in 3/95. When she passed away at age 77, we had a brain autopsy done and she had lewy body dementia.

I have always wondered whether the brain radiation did damage to her.

The medical center that treated her did admit it was possible.

I was her main caregiver during her cancer treatment and her dementia.

Her dementia and the years of it did so much damage to her mind and body.

Thank you for the very up to date and informative article on this topic.

I would expect no less from MSKCC.

Would you please contact me as I wish to know how to qualify for stem cell therapy. thank you.

Patrick, thank you for reaching out. Unfortunately, this stem cell therapy is still in an investigative stage and is not currently available in human trials. However, if you are interested in a consultation with an MSK physician, you can call 866-886-9807

or learn more at:

http://www.mskcc.org/research/brain-tumor/appointment

would these treatments be able to help pediatric patients who received radiation treatment thirty years ago and exhibit many of the complications associated w high levels of radiation? Thank you.

Kelly, thank you for reaching out. This stem cell therapy is still in an investigative stage and it is difficult to predict exactly when and how it might be used in patients. However, Memorial Sloan Kettering does have a specialized program for survivors of childhood and young adult cancers, called the Adult Long-Term Follow-Up Program, which might able to assist you. You can learn more at this link:

http://www.mskcc.org/pediatrics/adult-survivors-childhood

I am excited to see this and praying it goes to human trial. My son was diagnosed and treated for an atypical ependymoma in 2011. He was 6 at the time. He had a total resection and was treated with the max dose of radiation as his tumor was 3cm in diameter. He is now 11 and we have been told by 2 different doctors that he will stop walking, talking, eating and eventually die from the damage. He had hemiparesis on the left side of his body after surgery that had recovered 90%, but is now losing ambulation capabilities and has extensive short term memory damage. So praying this goes to human trial in time for our son.

This article is extremely interesting. Are there any recommendations for what can be done currently with functioning problems and quality of life issues.

I have increasing scarring to the brain as a result of radiation in 2009. My doctor has just told me about myelin damage and I have motor and cognitive symptoms. How do I find out more about this; and how do I let him know about it? He has tolde me there is no treatment. Is anyone else doing research on this problem?

We're sorry to hear you're having these side effects. The research discussed in this blog post is still at an early stage, and it's too soon to say whether it ultimately will prove beneficial to patients. We recommend you ask your oncologist for a referral to a rehabilitation specialist, who may be able to help you cope with many of the symptoms that you're experiencing. Thank you for your comment.

Has there been any progress in this area? Are you any closer to bringing this to clinical trials? I'm having an extremely difficult time after my two brain tumors in everyday life. I have no friends, my parents loathe me, I can't control my impulses, hold a job...

Dear Joe, we are very sorry to hear about your diagnosis and the impact treatment has had on your quality of life. If you would like to make an appointment with one of our specialists to discuss possible treatment options, including your eligibility to participate in one of our open clinical trials, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

Add new comment

We welcome your questions and comments. While we share many of them with our world-class doctors and researchers, we regret that in order to protect your privacy, we are not able to make personal medical recommendations on this forum, nor do we publish comments that contain your personal information. If you would like to consult with an MSK doctor, we encourage you to make an appointment at 800-525-2225 or request an appointment online.

Your email address is kept private and will not be shown publicly.