Mapping TBI improvement with MAPCs

DURHAM, N.C.—A preclinical study has revealed that a stem cell treatment known as Multipotent Adult Progenitor Cell (MAPC) therapy is capable of engendering lasting cognitive improvement in rat models of traumatic brain injury. Previous work had demonstrated that administering the adult progenitor cells following traumatic brain injury “provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment,” as noted in the study’s abstract, but its potential in recovering neurological function had not been explored until now. The work first appeared online in the STEM CELLS Translational Medicine Express issue Nov. 4.

The work was performed by a team of researchers from the University of Texas Medical School at Houston, led by Charles Cox, Jr., M.D., and scientists from Athersys, Inc., which is developing the stem cell therapy. The researchers injected rats with brain injuries with MAPC cells two hours after injury and 24 hours after injury, with one group receiving 2 million cells per kilogram and the second a dose five times as large.

Four months after treatment, the rats that received the higher MAPC dose continued to demonstrate less inflammation and improvement in cognitive function when subjected to tests to determine the level of balance and motor function as well as the ability to navigate a maze. The study noted that “Improvements in cognitive and motor function were accompanied by localized reduction in numbers of activated microglia 120 days after injury. Cellular therapy also improved spatial learning, information retention and memory retrieval.” In addition, later examination of the rats’ brains revealed better brain function than what was seen in those rats that received the lower MAPC dose.

“Although preliminary, these findings offer evidence that this cell therapy can attenuate chronic neuro-inflammation and improve long-term cognitive functioning after traumatic brain injury,” Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine, said in a press release.

Cox added that their work seems to indicate that administering MAPC therapy intravenously might be an option as a treatment for traumatic brain injury someday.

Traumatic brain injury results when someone’s head violently impacts or is struck by an object, and can result in a number of symptoms, such as headache, confusion, dizziness or fatigue, blurred vision or a change in sleep patterns. When the brain is injured, one of the many effects is the activation of microglia, an immune cell (macrophage) found in the brain and spinal cord. While the activation of these cells is necessary, as they help to “remove necrotic tissue and induce myelin repair,” the study notes that “Activated microglia, a part of the neuroinflammatory response, are known to affect neurons and subsequently behavior. Long-term persistent activation can cause further neurodegeneration and contribute to cognitive decline.”

The National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health notes that common disabilities associated with a severe traumatic brain injury include difficulties with cognition, communication and behavior or mental health. In addition, “little can be done to reverse the initial brain damage caused by trauma,” and that roughly half of patients with severe head injuries will require surgery to “remove or repair hematomas (ruptured blood vessels) or contusions (bruised brain tissue).” The NINDS notes that primary options for treatment after a brain injury include ensuring proper brain oxygenation and blood flow, while treating more serious issues involve physical, occupational and/or speech/language therapy. As such, a treatment that could mitigate or even undo some of the damage of a traumatic brain injury would be a significant benefit for the indication.

The study, “Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury,” was funded by a Small Business Innovation Research agreement with Athersys and grants from Brown Foundation Inc. and Children’s Memorial Hermann Hospital Foundation.