Appendix K. 
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stroke, either via endogenous neuronal precursors^°^ or transplanted 
neural stem cells. Evidence indicates that endogenous neurons 
and astrocytes may also secrete growth factors to induce 
differentiation of endogenous precursors. In addition, two studies 
now provide suggestive evidence that neural stem cells/neural 
progenitor cells may show low immunogenicity, being 
immunoprivileged on transplant, and raising the possibility for use 
of donor neural stem cells to treat degenerative brain conditions. 
Pluchino et ai.^°® recently used adult neural stem cells to test 
potential treatment of multiple sclerosis lesions in the brain. Using a 
mouse model of chronic multiple sclerosis — experimental immune 
encephalitis — ^they injected neural stem cells either intravenously or 
intracerebrally into affected mice. Donor cells entered damaged, 
demyelinated regions of the brain and differentiated into neuronal 
cells. Remyelination of brain lesions and recovery from functional 
impairment were seen in the mice. Neural stem cells have also been 
used to investigate potential treatments for Parkinson’s disease. 
Using experimentally-lesioned animals as models for Parkinson’s 
disease, human neural stem cells have been observed to integrate 
and survive for extended periods of time.^°^ Dopaminergic cells (the 
cells degenerated in Parkinson’s disease) can be induced in these 
systems, and neural stem cells are capable of rescuing and 
preventing the degeneration of endogenous dopaminergic 
neurons, also producing improved behavioral performance in the 
animals. In these studies, the data suggest that the transplanted 
neural stem cells did not participate to a large extent in direct 
formation of dopaminergic neurons, but rather secreted 
neuroprotective factors and growth factors that stimulated the 
endogenous neural cells. In this respect, infusion of transforming 
growth factor into the brains of Parkinson’s mice induced 
proliferation and differentiation of endogenous neuronal precursors in 
mouse brain. Following this potential for stimulation of 
endogenous neuronal cells. Gill et al. recently reported on a Phase I 
trial in which glial derived neurotrophic factor (GDNF) was infused 
into the brains of five Parkinson’s patients. After one year there 
was a 61% increase in the activities of daily living score, and an 
increase in dopamine storage observed in the brain. In a tantalizing 
clinical application with direct injection of neural stem cells, a 
Parkinson’s patient was implanted with his own neural stem cells, 
resulting in an 80% reduction in symptoms at one year after 
treatment. Further clinical trials are underway. 
The olfactory ensheathing glial (OEG) cell from olfactory bulb 
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