ROBUST GROWTH OF CHRONICALLY INJURED SPINAL-CORD AXONS INDUCED BY GRAFTS OF GENETICALLY-MODIFIED NGF-SECRETING CELLS

Little spontaneous regeneration of axons occurs after acute and chroni c injury to the CNS. Previously we have shown that the continuous loca l delivery of neurotropic factors to the acutely injured spinal cord i nduces robust growth of spinal and. supraspinal axons, In the present study we examined whether chronically injured axons also demonstrate s ignificant neurotrophin responsiveness. Adult rats underwent bilateral dorsal hemisection lesions that axotomize descending supraspinal path ways, including the corticospinal, rubrospinal, and cerulospinal tract s, and ascending dorsal spinal sensory projections. One to three month s later, injured rats received grafts of syngenic fibroblasts genetica lly modified to produce nerve growth factor (NGF). Control subjects re ceived unmodified cell grafts or cells transduced to express the repor ter gene beta-galactosidase, Three to five months after grafting, anim als that received NGF-secreting grafts showed dense growth of putative cerulospinal axons and primary sensory axons of the dorsolateral fasc iculus into the grafted lesion site. Growth from corticospinal, raphae spinal, and local motor axons was not detected. Thus, robust growth of defined populations of supraspinal and spinal axons can be elicited i n chronic stages after spinal cord injury by localized, continuous tra nsgenic delivery of neurotrophic factors. (C) 1997 Academic Press.