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.


CONCLUSIONS
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 newborns with mild-to-moderate HII.
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Stephen
S
Ashwal
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Nirmalya
N
Ghosh
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Christine I
CI
Turenius
Department of Psychology, Loma Linda University School of Behavioral Health, Loma Linda, California.
Melissa
M
Dulcich
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Christopher M
CM
Denham
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Beatriz
B
Tone
Department of Psychology, Loma Linda University School of Behavioral Health, Loma Linda, California.
Richard
R
Hartman
Sanford-Burnham Medical Research Institute, Program in Stem Cell & Regenerative Biology, La Jolla, California.
Evan Y
EY
Snyder
1] Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California [2] Division of Translational Studies, School of Behavioral Health, Loma Linda University School of Medicine, Loma Linda, California.
Andre
A
Obenaus
D000818:Animals; D001522:Behavior, Animal; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation; D051381:Rats; D012737:Sex Factors; D033581:Stem Cell Transplantation
D005290:Ferric Compounds; C000499:ferric oxide