Natural chemicals that assist healing may one day help transplanted adult stem cells integrate into an injured brain, helping children with cerebral palsy recover lost function, according to researchers at the Medical College of Georgia.
"We know that we can get stem cells into the brain and they will turn into brain cells but we really don't know how well they work," says Dr. James E. Carroll, chief of the MCG Section of Pediatric Neurology. "The cells probably do form synapses," he says of connections brain cells make so they can communicate. "But the question is: Will all this integrate into improved function?"
Dr. Carroll is principal investigator on a new grant from the American Heart Association and an existing grant from the National Institutes of Health that are using an animal model of cerebral palsy to identify the most effective way to transplant stem cells and possibly answer that question.
With this latest grant, Dr. Carroll, who also treats patients with cerebral palsy, wants to determine whether transplanted stem cells work best when the cells are injected directly into the brain along with these natural chemicals, called chemokines.
Chemokines are growth factors that attract white blood cells and are quickly summoned to the site of an injury, such as a brain injury that occurs in cerebral palsy. More recently, researchers have found that chemokines also seem to attract stem cells to an injury site. However, at least in an animal model of cerebral palsy, the healing chemicals are present for only a few days after injury, Dr. Carroll has shown.
"Chemokines are produced normally, naturally and briefly after a brain injury of some type as part of the healing process," Dr. Carroll says. "But probably there are not enough of them produced and they are not produced long enough to do what we want to do. So we are working on ways to get additional factor into the brain to promote the integration of new cells long after the injury has occurred."
When he began his studies several years ago, Dr. Carroll was putting stem cells from donor mice into the circulation of an animal model of cerebral palsy. Preliminary work had shown that stem cells migrated to the injury site, but his studies showed too few cells were making the journey. The two-year grant from the American Heart Association, will enable to him to explore whether a direct injection into the brain can help increase the number of cells where they are needed and if the extra chemokines help them become part of a better-functioning brain.
He'll try several direct approaches including injecting chemokines into the injury site first and stem cells second and taking the technically-easier route of injecting both at the same time. To enable this approach, Dr. Carroll will use a virus' ability to infect a cell to get chemokines inside stem cells before they are injected.
Although stem cells are immature cells coveted for their potential to become many different types of cells, donated stem cells may trigger an immune response, much like a transplanted organ. So Dr. Carroll also will compare the success of transplants that include the immunosuppressive agent, cyclosporine-A, to those that don't.
He'll also look at the bottom line: whether the motor skills of the animal model are improved following the transplant.
Since he began his studies of stem cell transplants, parents nationwide have asked when the technique will be available to help children. "I tell them we are working hard and making progress, but it is slow and there may be clinical trials in several years," Dr. Carroll says. Although he thinks there is potential for stem cell therapy to one day help restore function lost to the group of disorders known as cerebral palsy, many unanswered questions remain. One concern is whether these proliferating young cells might cause tumors. Also, cerebral palsy is not a single problem, but a complex disease in which virtually all brain cell types could need repair.
He noted that there is much parents and caregivers already do for children with cerebral palsy, including physical therapy along with botox injections and baclofen pumps to reduce debilitating spasticity that comes from confused communication to the muscles about whether they should relax or contract.
Cerebral palsy, which affects about 500,000 people in the United States, is defined as brain damage that occurs before or during birth. The number of people with the disorder has increased over the last 30 years as more premature babies survive. Its effects run the gamut, from barely detectable to devastating loss of motor control. The causes are diverse as well, including everything from oxygen deprivation during birth to prenatal infections.
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