Study finds stem cell combination therapy improves traumatic brain injury outcomes

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 neuronal cells in the central nervous system, 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 white blood cells—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 stem cells 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.

New Hope for Reversing the Effects of Spinal Cord Injury

Walking is the obvious goal for individuals who have a chronic spinal cord injury, but it is not the only one. Regaining sensation and continence control also are important goals that can positively impact an individual’s quality of life. New hope for reversing the effects of spinal cord injury may be found in a combination of stem cell therapy and physical therapy as reported in Cell Transplantation by scientists at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

“Our phase one/two clinical trial had one goal: to give patients who have no other treatment options some hope,” said Hatem E. Sabaawy, MD, PhD, an assistant professor of medicine in the molecular and regenerative medicine program at Robert Wood Johnson Medical School. “Early findings have concluded that we have met our goal and can improve the quality of life for individuals with spinal cord injuries by providing a safe treatment that restores some neurological function.”

Dr. Sabaawy led a clinical trial that included 70 patients who had cervical or thoracic spinal cord injuries and were previously treated for at least six months without response. The patients were randomized into two groups, both of which were given physical therapy treatment. One of the groups also received stem cells derived from their own bone marrow injected near the injury site. Using the American Spinal Injury Association Impairment (AIS) Scale, patients received neurological and physical evaluations monthly for 18 months to determine if sensory and motor functions improved.

“Of primary importance, there was a notable absence of side effects in patients treated with stem cells during the course of our investigation,” added Dr. Sabaawy, who also is a resident member of The Cancer Institute of New Jersey at Robert Wood Johnson Medical School.

None of the patients in the control group who received only physical therapy showed any improvement in sensory or motor function during the same time frame. Although the scale of injuries differed, all patients who were treated with a combination of bone-marrow derived stem cells and physical therapy responded to tactile and sensory stimuli as early as 4 weeks into the study. After 12 weeks, they experienced improvements in sensation and muscle strength, which was associated with enhanced potency and improved bladder and bowel control that eventually allowed patients to live catheter-free. Patients who showed improvement based on the AIS scale also were able to sit up and turn in their beds.

“Since the emergence of stem cells as a potential therapy for spinal cord injury, scientists have diligently sought the best application for using their regenerating properties to improve a patient’s mobility,” said Joseph R. Bertino, MD, University Professor of medicine and pharmacology, interim director, Stem Cell Institute of New Jersey and chief scientific officer at The Cancer Institute of New Jersey. “Dr. Sabaawy’s discovery that treatment is more successful when stem cell therapy is combined with physical therapy could provide a remarkable, and hopefully sustainable, improvement in the overall quality of life for patients with spinal cord injury.”

At the end of 18 months, 23 of the 50 patients who received both physical therapy and stem cell therapy showed a significant improvement of at least 10 points on the AIS scale. Several were able to walk with assistance. In addition, more gains were made in motor skill control by patients with thoracic spinal cord injuries, suggesting that patients with thoracic spinal cord injuries may respond better to the combined treatment.

Dr. Sabaawy however cautioned that more studies are needed with a larger number of patients to test different cell dose levels and intervals at which stem cell therapy should be delivered.

“Although a cure for spinal cord injury does not yet exist, it is clear that the regenerative and secretory properties of bone-marrow derived stem cells can improve symptoms of paralysis in some patients when coupled with the current standard of care that physical therapy provides,” said Dr. Sabaawy. “We will continue monitoring our patients for long-term safety effects of stem cell therapy and work to expand our research through a phase two clinical trial that can be conducted at multiple centers nationwide and internationally.”

(Image courtesy: University of Alberta, Faculty of Rehabilitation Medicine)

New technique to deliver stem cell therapy may help damaged eyes regain their sight

Engineers at the University of Sheffield have developed a new technique for delivering stem cell therapy to the eye which they hope will help the natural repair of eyes damaged by accident or disease. This could help millions of people across the world retain – or even regain - their sight.

In research published in the journal Acta Biomaterialia, the team describe a new method for producing membranes to help in the grafting of stem cells onto the eye, mimicking structural features of the eye itself. The technology has been designed to treat damage to the cornea, the transparent layer on the front of the eye, which is one of the major causes of blindness in the world.

Using a combination of techniques known as microstereolithography and electrospinning, the researchers are able to make a disc of biodegradable material which can be fixed over the cornea. The disc is loaded with stem cells which then multiply, allowing the body to heal the eye naturally.

“The disc has an outer ring containing pockets into which stem cells taken from the patient’s healthy eye can be placed,” explains EPSRC Fellow, Dr Ílida Ortega Asencio, from Sheffield’s Faculty of Engineering. “The material across the centre of the disc is thinner than the ring, so it will biodegrade more quickly allowing the stem cells to proliferate across the surface of the eye to repair the cornea.”

A key feature of the disc is that it contains niches or pockets to house and protect the stem cells, mirroring niches found around the rim of a healthy cornea. Standard treatments for corneal blindness are corneal transplants or grafting stem cells onto the eye using donor human amniotic membrane as a temporary carrier to deliver these cells to the eye. For some patients, the treatment can fail after a few years as the repaired eyes do not retain these stem cells, which are required to carry out on-going repair of the cornea. Without this constant repair, thick white scar tissue forms across the cornea causing partial or complete sight loss. The researchers have designed the small pockets they have built into the membrane to help cells to group together and act as a useful reservoir of daughter cells so that a healthy population of stem cells can be retained in the eye.