Sr. Winn et al., POLYMER-ENCAPSULATED CELLS GENETICALLY-MODIFIED TO SECRETE HUMAN NERVE GROWTH-FACTOR PROMOTE THE SURVIVAL OF AXOTOMIZED SEPTAL CHOLINERGIC NEURONS, Proceedings of the National Academy of Sciences of the United Statesof America, 91(6), 1994, pp. 2324-2328
Effective treatments for neurodegenerative disorders are limited by ou
r inability to alter the progression of the diseases. A number of prot
eins have specific neuroprotective activities in vitro; however, the d
elivery of these factors into the central nervous system over the long
term at therapeutic levels has been difficult to achieve. BHK cells e
ngineered to express and release human nerve growth factor were encaps
ulated in an immunoisolation polymeric device and transplanted into bo
th fimbria-fornix-lesioned rat brains add naive controls. In the lesio
ned rat brain, chronic delivery of human nerve growth factor by the en
capsulated BHK cells provided nearly complete protection of axotomized
medial septal cholinergic neurons. Human nerve growth factor continue
d to be released by encapsulated cells upon removal from the aspirativ
e site after 3 weeks or from normal rat striatum after 3 and 6 months
in vivo. Long-term encapsulated cell survival was confirmed by histolo
gic analysis. This encapsulated xenogeneic system may provide therapeu
tically effective amounts of a number of neurotrophic factors, alone o
r in combination, to virtually any site within the body.