Transduction of human neural progenitor cells using recombinant adeno-associated viral vectors

Human neural progenitor cells (hNPCs) represent an attractive source for cell therapy of neurological disorders. Genetic modification of hNPCs may allow a controlled release of therapeutic proteins, suppress immune rejection, or produce essential neurotransmitters. In search of an effective gene delivery vehicle, we evaluated the efficiency of a recombinant adeno-associated viral (rAAV) vector expressing enhanced green fluorescent protein (CAGegfp). Our study demonstrated that CAGegfp efficiently transduced both proliferating and differentiated hNPCs in vitro. EGFP expression was detected as early as 1 day after exposure to CAGegfp and was detectable for up to 4 months. Following transduction, the growth rate of hNPCs slowed down, but they were still able to differentiate into neurons and glia. Furthermore, CAGegfp-modified hNPCs survived, differentiated and expressed EGFP after transplanting into spinal cord of adult rats. Our results indicated that rAAV vectors might be a useful tool in hNPC-based cell and gene therapy for neurological disorders.