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However, like other stem cell-based therapies, survival of therapeutic NSCs after transplantation is currently suboptimal. One approach to prolonging cell survival is to transiently overexpress an antiapoptotic protein within the cells prior to transplantation. Here, we investigate the utility and safety of this approach using a clinically tested,<jats:italic>v<\/jats:italic>-<jats:italic>myc<\/jats:italic>immortalized, human NSC line engineered to contain the suicide gene, cytosine deaminase (CD-NSCs). We demonstrate that both adenoviral- and minicircle-driven expression of the antiapoptotic protein<jats:italic>Bcl-2<\/jats:italic>can partially rescue CD-NSCs from transplant-associated insults. We further demonstrate that the improved CD-NSC survival afforded by transient<jats:italic>Bcl-2<\/jats:italic>overexpression results in decreased tumor burden in an orthotopic xenograft glioma mouse model following administrations of intracerebral CD-NSCs and systemic prodrug. Importantly, no evidence of CD-NSC transformation was observed upon transient overexpression of<jats:italic>Bcl-2<\/jats:italic>. This research highlights a critical need to develop clinically relevant strategies to improve survival of therapeutic stem cell posttransplantation. 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