Irvine, Calif. -- Researchers at the UC Irvine Reeve-Irvine ResearchCenter have used adult human neural stem cells to successfullyregenerate damaged spinal cord tissue and improve mobility in mice.
The findings point to the promise of using this type of cells forpossible therapies to help humans who have spinal cord injuries. Studyresults appear online in the Proceedings of the National Academy ofSciences Early Edition.
In their study, Brian Cummings, Aileen Anderson and colleaguesinjected adult human neural stem cells into mice with limited mobilitydue to spinal cord injuries. These transplanted stem cellsdifferentiated into new oligodendrocyte cells that restored myelinaround damaged mouse axons. Additionally, transplanted cellsdifferentiated into new neurons that formed synaptic connections withmouse neurons.
Myelin is the biological insulation for nerve fibers that iscritical for maintenance of electrical conduction in the centralnervous system. When myelin is stripped away through disease or injury,sensory and motor deficiencies result and, in some cases, paralysis canoccur. Previous Reeve-Irvine research has shown that transplantation ofoligodendrocyte precursors derived from human embryonic stem cellsrestores mobility in rats.
"We set out to find whether these cells would be able torespond to the injury in an appropriate and beneficial way on theirown," Cummings said. "We were excited to find that the cells respondedto the damage by making appropriate new cells that could assist inrepair. This study supports the possibility that formation of newmyelin and new neurons may contribute to recovery."
Mice that received human neural stem cells nine days afterspinal cord injury showed improvements in walking ability compared tomice that received either no cells or a control transplant of humanfibroblast cells (which cannot differentiate into nervous systemcells). Further experiments showed behavioral improvements after eithermoderate or more severe injuries, with the treated mice being able tostep using the hind paws and coordinate stepping between paws whereascontrol mice were uncoordinated.
The cells survived and improved walking ability for at leastfour months after transplantation. Sixteen weeks after transplantation,the engrafted human cells were killed using diphtheria toxin (which isonly toxic to the human cells, not the mouse). This procedure abolishedthe improvements in walking, suggesting that the human neural stemcells were the vital catalysts for the maintained mobility.
This study differs from previous work using human embryonicstem cells in spinal cord injury because the human neural stem cellswere not coaxed into becoming specific cell types beforetransplantation.
"This work is a promising first step, and supports the need tostudy multiple stem cell types for the possibility of treating of humanneurological injury and disease," Anderson said.
Desiree L. Salazar and Mitra Hooshmand of UCI, Nobuko Uchidaand Stan J. Tamaki of StemCells Inc., and Robert Summers and Fred H.Gage of the Salk Institute of Biological Studies participated in thestudy. Adult human neural stem cells were provided by StemCells Inc. inPalo Alto, Calif. The National Institutes of Health and the ChristopherReeve Foundation provided funding support.
The Reeve-Irvine Research Center was established to study howinjuries and diseases traumatize the spinal cord and result inparalysis or other loss of neurologic function, with the goal offinding cures. It also facilitates the coordination and cooperation ofscientists around the world seeking cures for paraplegia, quadriplegiaand other diseases impacting neurological function. Named in honor ofChristopher Reeve, the center is part of the UCI School of Medicine.
This Reeve-Irvine Research Center study is part of a campuswideeffort at UCI to lay the groundwork for new treatments and curesthrough responsible exploration of stem cell research.
About the University of California, Irvine: Celebrating 40years of innovation, the University of California, Irvine is atop-ranked university dedicated to research, scholarship and communityservice. Founded in 1965, UCI is among the fastest-growing Universityof California campuses, with more than 24,000 undergraduate andgraduate students and about 1,400 faculty members. The second-largestemployer in dynamic Orange County, UCI contributes an annual economicimpact of $3 billion. For more UCI news, visit www.today.uci.edu.
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