Genetically Modified Cells

NSCs and NPCs are well suited as target populations for genetic (neurotrophic factors) and cellular therapy. A subclone of NSCs was transduced with a retrovirus encoding rat neuro-trophin-3 (NT-3) (47). The engineered NSCs successfully produced large amounts of NT-3 in vitro and in vivo. When cells from the NT-3-expressing NSC subclone were implanted into the infarct of hypoxic-ischemic brain, the percentage of donor-derived neurons was dramatically increased. Many of the neurons were calbindin positive; some were also gamma aminobutyric acid (GABA) ergic, glutamatergic, or cholinergic (48). Ex vivo-engineered NSCs with NT-3 also appear to differentiate into functional neurons.

Similarly, telomerized human BMSCs transfected with the BDNF gene with a fiber-mutant adenovirus vector improved recovery in rats after MCAO (49). Neurotrophic factors in addition to BDNF, e.g., glial cell-derived neurotrophic factor (GDNF), had a similar effect in this model. Rats that received BMSC-GDNF showed significantly more functional recovery than did control rats following MCAO, as demonstrated by improved behavioral test results and reduced ischemic damage on MRI. Thus, BMSC transfected with the BDNF or GDNF gene improve functional outcome and reduce ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.

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