GENE-TRANSFER TO THE CENTRAL-NERVOUS-SYSTEM BY TRANSPLANTATION OF CEREBRAL ENDOTHELIAL-CELLS

A cerebral endothelial immortalized cell line was used in transplantat ion experiments to deliver gene products to the adult rat brain. Survi val of grafted cells was observed for at least 1 year, without any sig n of tumor formation. When genetically modified to express bacterial b eta-galactosidase and transplanted into the striatum, these cells were shown, by light and electron microscope analysis, to integrate into t he host brain parenchyma and microvasculature. Following implantation into the striatum and nucleus basalis of adult rats, endothelial cells engineered to secrete mouse, beta-nerve growth factor (NGF) induced t he formation of a dense network of low-affinity NGF receptor-expressin g fibers near the implantation sites. This biological response was obs erved from 3 to 8 weeks after engraftment. The present study establish es the cerebral endothelial cell as an efficient vector for gene trans fer to the central nervous system.