The findings point to the promise of using this type of cells for possible therapies to help humans who have spinal cord injuries. Study results appear online in the Proceedings of the National Academy of Sciences Early Edition.
In their study, Brian Cummings, Aileen Anderson and colleagues injected adult human neural stem cells into mice with limited mobility due to spinal cord injuries. These transplanted stem cells differentiated into new oligodendrocyte cells that restored myelin around damaged mouse axons. Additionally, transplanted cells differentiated into new neurons that formed synaptic connections with mouse neurons.
Myelin is the biological insulation for nerve fibers that is critical for maintenance of electrical conduction in the central nervous system. When myelin is stripped away through disease or injury, sensory and motor deficiencies result and, in some cases, paralysis can occur. Previous Reeve-Irvine research has shown that transplantation of oligodendrocyte precursors derived from human embryonic stem cells restores mobility in rats.
"We set out to find whether these cells would be able to respond to the injury in an appropriate and beneficial way on their own," Cummings said. "We were excited to find that the cells responded to the damage by making appropriate new cells that could assist in repair. This study supports the possibility that formation of new myelin and new neurons may contribute to recovery."
Mice that received human neural stem cells nine days after spinal cord injury showed improvements in walking ability compared to mice that received either no cells or a control transplant of human fibroblast cells (which cannot differentiate into nervous system cells). Further experiments showed behavioral improvements after either moderate or more severe injuries, with the treated mice being able to step using the hind paws and coordinate stepping between paws whereas control mice were uncoordinated.
The cells survived and improved walking ability for at least four months after transplantation. Sixteen weeks after transplantation, the engrafted human cells were killed using diphtheria toxin (which is only toxic to the human cells, not the mouse). This procedure abolished the improvements in walking, suggesting that the human neural stem cells were the vital catalysts for the maintained mobility.
This study differs from previous work using human embryonic stem cells in spinal cord injury because the human neural stem cells were not coaxed into becoming specific cell types before transplantation.
"This work is a promising first step, and supports the need to study multiple stem cell types for the possibility of treating of human neurological injury and disease," Anderson said.
Desiree L. Salazar and Mitra Hooshmand of UCI, Nobuko Uchida and Stan J. Tamaki of StemCells Inc., and Robert Summers and Fred H. Gage of the Salk Institute of Biological Studies participated in the study. Adult human neural stem cells were provided by StemCells Inc. in Palo Alto, Calif. The National Institutes of Health and the Christopher Reeve Foundation provided funding support.
The Reeve-Irvine Research Center was established to study how injuries and diseases traumatize the spinal cord and result in paralysis or other loss of neurologic function, with the goal of finding cures. It also facilitates the coordination and cooperation of scientists around the world seeking cures for paraplegia, quadriplegia and other diseases impacting neurological function. Named in honor of Christopher Reeve, the center is part of the UCI School of Medicine.
This Reeve-Irvine Research Center study is part of a campuswide effort at UCI to lay the groundwork for new treatments and cures through responsible exploration of stem cell research.
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Journal
Proceedings of the National Academy of Sciences