Implants of polymer-encapsulated XXXX NGF-secreting cells in the nonhuman primate: rescue and sprouting of degenerating cholinergic basal forebrain neurons.

@entity1 @entity7169 @entity75 @entity5434 @entity5381 @entity1877 @entity179 @entity195 @entity2057 @entity528
Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of @entity1 nerve growth factor (BHK-hNGF). Following polymer encapsulation, these cells were implanted into the lateral ventricle of four @entity5434 immediately following a unilateral transection/aspiration of the fornix. Three control monkeys received identical implants, with the exception that the BHK cells were not genetically modified to secrete hNGF and thus differed only by the hNGF construct. One monkey received a fornix transection only. All monkeys displayed complete transections of the fornix as revealed by a comprehensive loss of acetylcholinesterase-containing fibers within the hippocampus @entity75 . Control monkeys that were either unimplanted or received BHK-control (non-NGF secreting) cell implants did not differ from each other and displayed extensive losses of @entity1877 acetyltransferase and p75 NGF receptor ( @entity7169 )-immunoreactive neurons within the @entity5381 ( @entity5381 ; 53 and 54%, respectively) and vertical limb of the diagonal band (VLDB; 21 and 30%, respectively) @entity75 . In contrast, monkeys receiving implants of BHK-hNGF cells exhibited a only a modest loss of cholinergic neurons within the septum (19 and 20%, respectively) and VLDB (7%). Furthermore, only implants of hNGF-secreting cells induced a dense sprouting of cholinergic fibers within the septum, which ramified against the ependymal lining of the ventricle adjacent to the transplant site. Examination of the capsules retreived from monkeys just prior to their death revealed an abundance of cells that produced detectable levels of hNGF in a sufficient concentration to differentiate PC12A cells in culture. These findings support the use of polymer-encapsulated cell therapy as a potential treatment for @entity179 such as @entity195 where @entity528 is a consistent pathological feature. Moreover, this encapsulated xenogeneic system may provide therapeutically effective levels of a number of @entity2057 , alone or in combination, to select populations of neurons within the central nervous system.
