Researchers from the University of California, San Diego (UCSD) School of Medicine are reporting that six weeks after receiving grafts of human spinal stem cells (hSSCs), paralyzed rats regained almost normal ambulatory function. The animals were paralyzed due to loss of blood flow. The study has been published in the June 29, 2007 edition of Neuroscience. UC San Diego professor of anesthesiology Dr. Martin Marsala, M.D. led the study.
“We demonstrated that when damage has occurred due to a loss of blood flow to the spine’s neural cells, by grafting human neural stem cells directly into the spinal cord we can achieve a progressive recovery of motor function,” said Marsala.
“This could some day prove to be an effective treatment for patients suffering from the same kind of ischemia-induced paralysis.”
Marsala hopes to be prepared to carry out human clinical trials by next year. The current focus is on using animal models to establish effectiveness and safety of the human stem cell therapy.
For those individuals who undergo aortic cross-clamping, 20 to 40 percent of patients experience spinal cord ischemia as a consequence of the surgical procedure. It is a serious complication and causes paraplegia. During the procedure to correct a potentially lethal aneurysm, blood flow from the heart must be temporarily blocked with a clamp as the surgeon works on the aorta. Even though the spinal cord remains intact, loss of muscle control or irreparable rigidity and spasticity of the lower limbs can occur due to the lack of blood flow that results in the death of spinal inhibitory neurons which are specialized spinal cord neurons. After only 30 minutes, the neurons become susceptible to death.
“The important difference between spinal cord ischemia and spinal cord trauma, such as might occur in a diving or car accident, is that in the ischemia model, no mechanical damage has occurred to the spinal cord,” said Marsala.
“The spinal cord and brain motor centers are still partially connected, but there has been a selective loss of inhibitory neurons in the spinal cord. Since these cells are necessary for coordinated motor activity, our research aims to replace these lost neurons by grafting new spinal stem cells, which repopulates the pool of degenerated neurons.”
Human spinal stem cells were injected into nine rats 21 days after spinal cord ischemia was induced. There were a total of 16 rats used in the study and the seven non-stem cell rats were injected with a placebo medium containing no stem cells. Every seven days the motor function was recorded and in the rats that received stem cells, a progressive recovery of ambulatory functions was observed.
In all lower extremity joints, three of the nine rats injected with hSSC’s improved their mobility, but most compelling was that another three actually returned to walking after six weeks. According to Marsala, in all nine rats, the majority of transplanted human spinal stem cells survived and became mature neurons. In the spinal area, all the animals had a constant presence of transplanted cells and compared to the control group the hSSC’s rats all achieved significantly better motor scores. Similar results were achieved during a second study which was conducted over three-months.
“Other human stem cell transplants in the spinal cord have focused on repairing the myelin-forming cells,” said co-author Karl Johe, a researcher at Neuralstem, the company that manufactures the hSSCs used in the study. “In this study, we succeeded at reconstructing the neural circuitry, which had not been done before.”
The researchers believe that the therapy may eventually be confirmed to be even more successful in human patients, who would be able to receive physical therapy once treated.
Saying that the goal is to offer a significant gain in functional mobility of the patient’s legs Johe added that, “physical therapy may accelerate integration of the grafted stem cells and enhance their therapeutic benefit.”
Marsala has a history working with human neuronal stem cells. A previous work also using rat models was published in the October 2004 issue of the European Journal of Neurosciences. 40 to 50 percent of the animals tested in that study had significant improvement in motor function. The progress was measured by recording improved muscle tone and the suppression of spastic movements. In the spinal cords of the rats that received transplanted neuronal cells, a post-mortem study showed an increase in the expression of inhibitory neurotransmitters and a robust maturation of neurons.
Spinal drug treatments using implanted pumps or continuous systemic drugs make up the current and somewhat effective standard treatment for debilitating muscle spasticity. These treatments are susceptible to eventual drug tolerance which lessens their efficacy, and are also accompanied by side effects.
“These research findings could offer great hope to people with spinal ischemic injury who suffer from resulting spasticity and rigidity,” said Marsala.
