The Reparative Effects of Neural Stem Cells in Neonatal Hypoxic Ischemic Injury are Not Influenced by Host Gender

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 hypoxia-ischemic injury (HII) model, treated with human female neural stem cells (hNSCs), labeled with superparamagnetic iron-oxide (SPIO) particles implanted into the contralateral cerebral ventricle. We monitored HII evolution (by MRI, 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 90d) or behavior (90d). SPIO 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. CONCLUSIONS—Our results suggest that hNSC treatment (including using hNSCs that are prelabeled with iron to allow tracking in real time by MRI) would be equally safe and effective for male and female human newborns with mild-to-moderate HII. Users may view, print, copy, download and text and datamine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Corresponding author: Stephen Ashwal MD, Division of Pediatric Neurology, Department of Pediatrics, Loma Linda University School of Medicine, 11175 Campus St, Room 1120G, Loma Linda, CA 92350, Tel: (909) 558-8242; Fax: (909) 558-0479 [email protected]. Financial Disclosures: None of the authors have any financial disclosures relevant to this study. HHS Public Access Author manuscript Pediatr Res. Author manuscript; available in PMC 2015 April 20. Published in final edited form as: Pediatr Res. 2014 May ; 75(5): 603–611. doi:10.1038/pr.2014.7. A uhor M anscript