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The injured adult central nervous system exhibits very little capacity to regenerate after spinal cord injury.In contrast,grafts of neural stem cells to sites of spinal cord injury extend extremely large numbers of axons over very long distances (at least 50 mm).Notably,while regeneration of injured adult axons is severely restricted in spinal cord white matter,myelin actually stimulates the growth of axons emerging from neural stem cell grafts,a finding that is related to the expression of specific cell surface antigens on myelin that interact with stem cell-derived axons.We have recently found that implants of neural stem cells also enable the regeneration of injured host axons into the spinal cord lesion site (filled with a neural stem cell graft).The most important axonal system for the control of voluntary movement in humans is the corticospinal projection,yet this system that has been refractory to most efforts promotes its regeneration.However,when neural stem cells are driven to caudal neural (i.e.,spinal cord) fates and implanted into sites of spinal cord injury,corticospinal axons regenerate in large numbers into the lesion site.Mouse,rat and non-human primate corticospinal axons all exhibit similar responses to implants of caudalized neural stem cell grafts.Within the lesion,regenerating corticospinal axons form synap-tic connections with grafted neural stem cells;these grafts in turn extend axons caudal to the injury site and form synapses with the host.In this manner,a synaptic relay is formed across the injury site that in some models supports improvement in functional outcomes.We are currently exploring cellular and molecular mechanisms underlying this extraordinary degree of axonal growth,while attempting to develop practical methods for possible application to human clinical trials.(Supported by CIRM,Veterans Administration,NIH,Craig H.Neilsen Foundation,Wings for Life).