EX-VIVO GENE DELIVERY OF PLATELET-DERIVED GROWTH-FACTOR INCREASES O-2A PROGENITORS IN ADULT-RAT SPINAL-CORD

The O-2A progenitor cell, which serves as a stem cell for the myelinat ing oligodendrocyte, has been implicated as a major target for radiati on-induced spinal cord injury. In an attempt to increase the number of O-2A cells in the spinal cord, we applied an ex vivo gene therapy pro cedure for delivering platelet-derived growth factor (PDGF). Recombina nt fibroblasts expressing PDGF A chain were injected into the cisterna magna of adult rats, which resulted in cell seeding of the subarachno id space of the cervical spinal cord. The number of O-2A progenitors i n the cervical spinal cord was then assessed with an in vitro clonogen ic assay. O-2A cells were found to be increased 8 days after recombina nt cell injection,and they remained elevated up to at least 14 days. A nalysis of O-2A colonies indicated that the implantation of PDGF-expre ssing cells increased the number of O-2A progenitors without affecting their in vitro proliferation potential or differentiation capacity. T hese data suggest that implantation of PDGF-expressing cells in the su barachnoid space of the cervical spinal cord may influence a stem cell population critical to the repair of demyelinated lesions.