Significance Spinal cord injury is a common and debilitating human disease for which currenttreatments are unsatisfactory. In rodent studies, we have shown that grafts of cells genetically modified to produce nervous system growth factors can elicit robust growth of axons and, in some cases, functional recovery after spinal cord injury. In the present experiments, we are determining whether grafts of autologous primate cells genetically modified to produce neurotrophic factors will promote axonal growth and functional amelioration in the primate spinal cord. Positive findings from these experiments could lead to new treatments for human spinal cord injury. Objectives Examine whether grafts of autologous fibroblasts genetically modified to produce nerve growth factor (NGF) to the unlesioned primate spinal cord elicit axonal growth. It will be determined whether principles of neurotrophism observed in the rodent spinal cord are replicated in the primate spinal cord. Previous studies in rodents have demonstrated that grafts of NGF-producing genetically modified cells elicit robust growth of primary sensory axons and coerulospinal axons in the unlesioned rat spinal cord. Before beginning partial lesion experiments in primates, this aim will first determine whether NGF-producing cell grafts to the intact spinal cord also elicit growth, both to provide evidence that neurotrophic factor principles are valid in primates, and to justify proceeding to partial lesion experiments. Results Grafts of NGF-secreting cells elicited robust growth of sensory and coerulospinal axons in the primate spinal cord, thereby establishing the validity of neurotrophic factor principles in primates. Future Directions Determine whether grafts of fibroblasts genetically modified to produce neurotrophin-3 (NT-3) to the partially lesioned primate spinal cord elicit axonal growth and functional recovery. KEYWORDS gene therapy, spinal injury,
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