Study finds stem cell combination therapy improves traumatic brain injury outcomes

March 20, 2014

Traumatic brain injuries (TBI), sustained by close to 2 million Americans annually, including military personnel, are debilitating and devastating for patients and their families. Regardless of severity, those with TBI can suffer a range of motor, behavioral, intellectual and cognitive disabilities over the short or long term. Sadly, clinical treatments for TBI are few and largely ineffective.

In an effort to find an effective therapy, neuroscientists at the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery in the USF Health Morsani College of Medicine, University of South Florida, have conducted several preclinical studies aimed at finding combination therapies to improve TBI outcomes.

In their study of several different therapies—alone and in combination—applied to laboratory rats modeled with TBI, USF researchers found that a combination of human umbilical cord blood cells (hUBCs) and granulocyte colony stimulating factor (G-CSF), a growth factor, was more therapeutic than either administered alone, or each with saline, or saline alone.

The study appeared in a recent issue of PLoS ONE.

"Chronic TBI is typically associated with major secondary molecular injuries, including chronic neuroinflammation, which not only contribute to the death of in the , but also impede any natural repair mechanism," said study lead author Cesar V. Borlongan, PhD, professor of neurosurgery and director of USF's Center of Excellence for Aging and Brain Repair. "In our study, we used hUBCs and G-CSF alone and in combination. In previous studies, hUBCs have been shown to suppress inflammation, and G-CSF is currently being investigated as a potential therapeutic agent for patients with stroke or Alzheimer's disease."

Their stand-alone effects have a therapeutic potential for TBI, based on results from previous studies. For example, G-CSF has shown an ability to mobilize stem cells from bone marrow and then infiltrate injured tissues, promoting self-repair of neural cells, while hUBCs have been shown to suppress inflammation and promote cell growth.

The involvement of the immune system in the central nervous system to either stimulate repair or enhance molecular damage has been recognized as key to the progression of many neurological disorders, including TBI, as well as in neurodegenerative diseases such as Parkinson's disease, multiple sclerosis and some autoimmune diseases, the researchers report. Increased expression of MHCII positive cells—cell members that secrete a family of molecules mediating interactions between the immune system's —has been directly linked to neurodegeneration and cognitive decline in TBI.

"Our results showed that the combined therapy of hUBCs and G-CSF significantly reduced the TBI-induced loss of neuronal cells in the hippocampus," said Borlongan. "Therapy with hUBCs and G-CSF alone or in combination produced beneficial results in animals with experimental TBI. G-CSF alone produced only short-lived benefits, while hUBCs alone afforded more robust and stable improvements. However, their combination offered the best motor improvement in the laboratory animals."

"This outcome may indicate that the had more widespread biological action than the drug therapy," said Paul R. Sanberg, distinguished professor at USF and principal investigator of the Department of Defense funded project. "Regardless, their combination had an apparent synergistic effect and resulted in the most effective amelioration of TBI-induced behavioral deficits."

The researchers concluded that additional studies of this combination therapy are warranted in order to better understand their modes of action. While this research focused on motor improvements, they suggested that future combination therapy research should also include analysis of cognitive improvement in the laboratory animals modeled with TBI.

Explore further: Researchers find long-term consequences for those suffering traumatic brain injury

More information: Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, Song S, Kaneko Y, Borlongan CV. (2014) Combination Therapy of Human Umbilical Cord Blood Cells and Granulocyte Colony Stimulating Factor Reduces Histopathological and Motor Impairments in an Experimental Model of Chronic Traumatic Brain Injury. PLoS ONE 9(3): e90953. DOI: 10.1371/journal.pone.0090953

Related Stories

Researchers find long-term consequences for those suffering traumatic brain injury

January 4, 2013
Researchers from the University of South Florida and colleagues at the James A. Haley Veterans' Hospital studying the long-term consequences of traumatic brain injury (TBI) using rat models, have found that, overtime, TBI ...

Study examines amyloid deposition in patients with traumatic brain injury

November 11, 2013
Patients with traumatic brain injury (TBI) had increased deposits of β-Amyloid (Aβ) plaques, a hallmark of Alzheimer Disease (AD), in some areas of their brains in a study by Young T. Hong, Ph.D., of the University of Cambridge, ...

Skull resconstruction immediately following traumatic brain injury worsens brain damage

March 22, 2012
Immediate skull reconstruction following trauma that penetrates or creates an indentation in the skull can aggravate brain damage inflicted by the initial injury, a study by a University of South Florida research team reports. ...

Stem cells help repair traumatic brain injury by building a 'biobridge'

October 3, 2013
University of South Florida researchers have suggested a new view of how stem cells may help repair the brain following trauma. In a series of preclinical experiments, they report that transplanted cells appear to build a ...

Researchers study factors affecting self-reporting among people with TBI

February 26, 2014
West Orange, NJ. February 26, 2014. Kessler Foundation researchers have found that among individuals with TBI, depression and self-awareness affect subjective reports of memory, quality of life (QOL), and satisfaction with ...

Can mild hypothermia treatment improve neuron survival after traumatic brain injury?

September 23, 2013
Moderate reductions in body temperature can improve outcomes after a person suffers a traumatic brain injury (TBI). New research that identifies positive effects of mild hypothermia on brain tissue is presented in an article ...

Recommended for you

The neural codes for body movements

July 21, 2017
A small patch of neurons in the brain can encode the movements of many body parts, according to researchers in the laboratory of Caltech's Richard Andersen, James G. Boswell Professor of Neuroscience, Tianqiao and Chrissy ...

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.