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Stem Cells     

This is one of a series of stories in This Week on stem cell work underway at UCSD

Stem Cell Research Holds Promise
for Victims of Spinal Cord Ischemia

By Debra Kain | March 13, 2006

Dr. Martin Marsala

Dr. Martin Marsala, an associate professor in the department of anesthesiology, hopes his research with stem cells will one day soon allow people who are suffering from spinal ischemic injury to improve their motor function.

His research focuses on is developing cell-replacement therapies aimed at re-populating pools of inhibitory neurons lost when blood supply to the spinal cord is blocked during surgery. While Marsala's research to date has been with rats and mini-pigs, his work is moving towards human trials within the next one to two years, with the goal of promoting motor recovery after spinal cord ischemia.

Paraplegia from spinal cord ischemia is a serious complication that occurs in 20 to 40% of patients undergoing a surgical process called aortic cross-clamping. When the surgeon works on the aorta to correct a potentially lethal aneurysm, this large vessel carrying all of the blood flow from the heart must be temporarily blocked. When this clamping occurs for more than 30 minutes, the procedure can result in the loss of specialized spinal cord neurons called spinal inhibitory neurons. Loss of these neurons can lead to irreversible spasticity and rigidity, or loss of muscle control, in the lower limbs.

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UCSD Stem Cells site

“The important difference between spinal cord ischemia and spinal trauma, such as might occur in a diving or car accident, is that no mechanical damage has occurred to the spinal cord,” said Marsala. “Connectivity between the spinal cord and brain motor centers is present, but there has been a selective loss of small inhibitory neurons in the spinal cord that are necessary for coordinated motor activity. Our research aims to replace these lost neurons by grafting spinal stem cells.”

In work published in October 2004 in the European Journal of Neurosciences, Marsala studied immuno-suppressed rat models that were grafted with human hNT neurons. Significantly improved motor function – measured by a suppression of spastic movements and improved muscle tone – was shown in 40 to 50% of the animals.

“In short, many of the rats regained their ability to walk due to suppression of spastic hypertonia,” said Marsala.

During a 12-week period in which the animals were followed, the UCSD team found that rats receiving neuronal cell transplants displayed a progressive recovery of motor function and a decrease in spasticity in the lower extremities over a period of several weeks following the injections. Fifty percent of the animals experienced a significant improvement in motor function. In contrast, the “control” rats that did not receive neuron transplants exhibited no improvement in motor function or spasticity. A post-mortem study of the animals showed a robust maturation of neurons and an increase in the expression of inhibitory neurotransmitters in the spinal cords of rats that received the transplanted neuronal cells.

“These findings provided conclusive evidence that transplantation of human neuronal cells into a specific region of the spinal cord can be an effective treatment for spasticity and rigidity in cases of ischemic spinal cord injury,” said Marsala.

Since then, the UCSD team has continued the neuronal stem cell studies using a rat model of spinal ischemic injury and human spinal stem cells. In addition, Marsala recently completed pre-clinical dosing and safety studies using mini-pigs in studies conducted in the Czech Republic in collaboration with Dr.Jan Motlik, a veterinarian from Institute of Genetics and Animal Physiology in Libechov.

“We looked to find the optimal number of stem cells to graft and to define the safety of the procedure before moving to clinical trials using humans,” Marsala said.

Based on the successful research results using the mini-pigs, he and his collaborators are optimistic of receiving permission to move ahead with these trials.

Marsala is confident that those patients affected by spinal cord ischemia will be willing to try the stem cell treatment. Current treatment for debilitating muscle spasticity is continuous systemic or spinal drug treatments using implanted pumps. These approaches, while displaying satisfactory efficacy, are often accompanied by side effects and eventual drug tolerance.

“This treatment offers hope to people with spinal ischemic injury who suffer from resulting spasticity and rigidity,” said Marsala.

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