Reparative effects of neural stem cells in neonatal rats with hypoxic-ischemic injury are not influenced by host sex

BACKGROUND: Gender is increasingly recognized as an important influence on brain development, disease susceptibility, and response to pharmacologic/rehabilitative treatments. In regenerative medicine, it remains entirely unknown whether there is an interaction between transplanted stem cells and host gender that might bias efficacy and safety in some patients but not others. METHODS: We examined the role of recipient gender in a neonatal rat hypoxic-ischemic injury (HII) model, treated with female human neuronal stem cells (hNSCs), labeled with superparamagnetic iron oxide particles implanted into the contralateral cerebral ventricle. We monitored HII evolution (by magnetic resonance imaging, histopathology, behavioral testing) and hNSC fate (migration, replication, viability). RESULTS: Recipient gender after implantation did not influence the volume or location of ischemic injury (1, 30, or 90 d) or behavior (90 d). Superparamagnetic iron oxide labeling did not influence HII evolution. Implantation had its greatest benefit on mild/moderate injuries, which remained stable rather than increasing as in severe HII as is the natural history for such lesions. CONCLUSION: Our results suggest that hNSC treatment (including using hNSCs that are prelabeled with iron to allow tracking in real time by magnetic resonance imaging) would be equally safe and effective for male and female human new-borns with mild-to-moderate HII.