June 17, 2003 Tampa, FL (June 12, 2003) -- Stem cells derived from human umbilical cord blood (HUCB) migrate to damaged areas in the brain and spinal cord caused by disease or injury and provide some therapeutic benefit, two new animal studies by researchers at the University of South Florida Center of Excellence in Aging and Brain Repair found.
Both studies, conducted in collaboration with Saneron CCEL Therapeutics, Inc., appear in the most recent issue of the Journal of Hematotherapy & Stem Cell Research published today.
The first study, featured on the cover, reports that cord blood cells administered intravenously delayed disease progression and improved the survival of mice genetically programmed to develop amyotrophic lateral sclerosis (ALS). The cells found their way not only to regions of the brainstem, brain and spinal cord attacked by ALS, but also circulated to organs outside the central nervous system such as the lungs, heart and spleen.
The second study demonstrated that intravenous injections of HUCB cells were drawn directly to the site of trauma in rats with spinal cord injuries and helped restore some motor function.
"We were surprised to find so many of these human cells throughout the body three months after transplant," said Svitlana Garbuzova-Davis, PhD, DSc, assistant professor of neurosurgery and first author of the cover article. "But it's a good sign, because it means the cells multiplied and survived quite a long time."
"This is one of the first studies to show the therapeutic potential of human umbilical cord blood cells in ALS, a neurodegenerative disease model rather than a trauma or injury model," said Paul R. Sanberg, PhD, DSc, a study author and director of the USF Center for Aging and Brain Repair. "More research is needed to determine the optimal amount of cells to provide better functional recovery and how these cells work in slowing progression of the disease."
ALS, also known as Lou Gehrig's Disease, attacks the nerve cells responsible for controlling voluntary movement, known motor neurons, and eventually paralyzes even the muscles that control breathing. There is no cure for the fatal disease.
Implanting neural stem cells surgically is widely considered an unrealistic option for ALS because motor neuron damage spreads across several regions -- the brain, brainstem and spinal cord -- and would require too many complex targets for transplant.
Dr. Garbuzova-Davis, Dr. Sanberg and colleagues examined the therapeutic potential of infusing HUCB stem cells -- a more readily accessible alternative to embryonic neural stem cells -- into a mouse model for ALS. One group of mice received HUCB cells and the other was administered a solution without HUCB cells. Both groups received infusions before they showed the first symptoms of ALS.
The researchers demonstrated that the HUCB cells delayed disease progression, including weight loss, problems with balance and walking, and hind limb paralysis, by at least two to three weeks in treated mice -- an interval equal to about two years in humans. The HUCB treated mice also survived longer than the untreated mice.
Symptom delay was not primarily prompted by HUCB cells replacing damaged neural cells, Dr. Garbuzova-Davis said, because so few HUCB cells in the brain and spinal cord actually expressed characteristics of neurons and glial cells. Instead, the researchers suggest, the HUCB cells may somehow regulate the immune system, protecting remaining motor neurons from further damage and death.
The second study, by the USF Center for Aging and Brain Repair and Chosun University Medical School in Korea, reported the first use of HUCB stem cells for repair of spinal cord injury.
Samuel Saporta, PhD, USF professor of anatomy and neurosurgery, and colleagues, including Dr. Sanberg, infused HUCB stem cells into three groups of rats with spinal cord injuries and studied the effects on trauma-related behavioral impairment. One group was administered HUCB cells 24 hours following injury, another received cells five days after injury (delayed treatment), and the third, a control group, received no cellular treatment.
The researchers showed that the cells targeted the areas of injury in the spinal cord and led to some recovery of function, even when administered five days after injury. In fact, the delayed treatment group demonstrated more significant improvement in hind limb movement than either the rats treated at one day or the untreated rats. None of the rats walked following treatment with the dose of HUCB cells administered in this study.
The researchers suspect the better recovery results in animals with delayed treatment may be due to a less hostile immune environment as time passes. Immediately following injury, Dr. Saporta said, inflammatory substances called cytokines recruit immune cells to clear all foreign material away from the area of injury -- including, perhaps some of the infused HUCB cells.
"These cells have an amazing affinity for going where they are needed and take up residence within the nervous system," Dr. Saporta said. "Our results indicate that cord blood stem cells may provide a useful and novel treatment option for patients with spinal cord injury, but more studies are needed."
Both research groups plan further studies to investigate if and how the HUCB cells affect long-term repair of motor neurons.
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