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The Journal of Neuroscience, May 11, 2005, 25(19):4694-4705; doi:10.1523/JNEUROSCI.0311-05.2005
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Development/Plasticity/Repair
Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Remyelinate and Restore Locomotion after Spinal Cord Injury
Hans S. Keirstead,1 Gabriel Nistor,1 Giovanna Bernal,1 Minodora Totoiu,1 Frank Cloutier,1 Kelly Sharp,1 andOswald Steward1,2,3 Departments of 1Anatomy and Neurobiology, 2Neurobiology and Behavior, and 3Neurosurgery, Reeve-Irvine Research Center, College of Medicine, University of California at Irvine, Irvine, California 92697-4292
Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.
Key words: predifferentiation; transplantation; acute; chronic; remyelination; functional recovery; rat
Received Sep 22, 2004; revised March 28, 2005; accepted March 30, 2005.
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