Targeting the bone marrow to drive brain repair after radiation injury

December 4, 2017

Researchers leverage a link between the bone marrow and brain regeneration, aiming to improve outcomes for brain tumor patients with radiation injury

bone-marrow-brain-tissue
A cell from the bone marrow (green) has entered the brain via the bloodstream and fully integrated into the existing brain tissue (cell nuclei shown in blue). The bone marrow-derived cell, positive for a marker found on immune cells (red), promotes brain repair following radiation injury. (Image courtesy of Jorg Dietrich.)

 

By Jessica Lau

Harvard Stem Cell Institute researchers at the Harvard Department of Stem Cell and Regenerative Biology and the Center for Regenerative Medicine at Massachusetts General Hospital (MGH) have uncovered a novel connection between the bone marrow and brain regeneration following injury from radiation. In their new study, they found that cells from the bone marrow were carried by the blood to the brain after radiation injury, a process that promoted brain repair in animal models. Moreover, this regenerative activity was strengthened by a drug that is currently used in the clinic.

Their findings were reported in the Journal of Clinical Investigation on Dec. 4.

When patients with brain tumors undergo radiation therapy, they can develop serious complications. Brain injury from radiation can lead to cognitive impairments—such as problems with memory, attention, and concentration—as well as mood changes. “These complications are devastating for the patients and their families,” said David Scadden, MD, Gerald and Darlene Jordan Professor of Medicine at Harvard University, Director of the MGH Center for Regenerative Medicine, and senior author of the study. “We thought that it would be very valuable if we could identify ways to alter the outcomes for these people.”

The researchers first identified a link between the bone marrow and brain repair. They reasoned that as blood moves in and out of the brain, cells that are carried to the brain might impact its response to radiation injury. Indeed, in mice exposed to radiation, bone marrow cells moved into the blood and were carried to the brain, where they promoted the proliferation of brain cells. The bone marrow-derived cells displayed characteristics of macrophages, immune cells that clean up debris and foreign substances, and integrated into the brain tissue over time to have a long-term effect.

Notably, the bone marrow-derived cells moved to the brain in response to the hormone granulocyte-colony stimulating factor, or G-CSF. G-CSF is currently used as a drug to boost patients’ white blood cell levels that have fallen due to chemotherapy. Because of this observation, the researchers tested the ability of G-CSF to augment the brain repair activity of the bone marrow-derived cells.

When the researchers gave G-CSF to mice that had received radiation, the animals demonstrated improved recovery. Magnetic resonance imaging (MRI) scans showed that the mice had improved brain tissue density, comparable to levels in mice that did not undergo radiation. Additionally, a variety of behavioral tests showed that mice treated with G-CSF had improved cognitive function and memory.

“Having a potential strategy to improve the recovery of brain function in cancer patients and to prevent treatment-related side effects is very exciting,” said Jorg Dietrich, MD, PhD, Clinical Director of the Cancer Neurotoxicity Clinic and Brain Repair Research Program, MGH Cancer Center, who led the study along with Ninib Baryawno, PhD.

Because G-CSF is an FDA-approved drug, the timeline for bringing the study’s findings directly to patients can be expedited. “We are currently in the process of developing a clinical trial that could be open for enrollment within the next year,” said Dietrich. “It would allow us to study the potential use of G-CSF in promoting brain regeneration and improving neurocognitive symptoms in cancer patients.”