Age and sex differences in neural stem cell transplantation: a descriptive study in rats

PURPOSE: The purpose of this study was to determine whether neural stem cell (NSC) sexual dimorphism previously demonstrated in vitro translates in vivo in NSC transplantation experiments and constitutes a defining factor of the transplantation outcome. METHODS: NSCs isolated from the subventricular zone of 2-day-old or 20-month-old male and female rats were grown as neurospheres prior to being transplanted in the striatum of 2-day-old or 20-month-old male and female recipient animals. The outcome of the transplantation and the NSC differentiation status were analyzed 8 weeks later by assessing the expression of the markers doublecortin (DCX) for neuroblasts, glial fibrillary acidic protein (GFAP) for astrocytes, nestin for stem cells, and choline acetyltransferase (ChAT) for neuronal cholinergic phenotype by immunofluorescence. RESULTS: No NSCs were detected in the brain of rat pups 8 weeks after transplantation. However, the endogenous neurogenesis was dramatically increased in a sex-dependent manner. These data suggest that the transplanted NSCs may have triggered endogenous neurogenesis by the intermediate growth factors they may have produced or the production they may have induced. However, NSCs transplanted into the striatum of adult rats were detectable at week 8. NSC survival was dependent on the sex and age of the donor and the recipient. Some of the transplanted cells were found to express DCX, GFAP, and ChAT, supporting an ongoing differentiation process toward astroglial and neuronal cholinergic phenotypes. CONCLUSION: The outcome of the NSC transplantation was highly dependent on the sex and age of the combination donor/recipient. Data generated from our work may allow us in the future to answer the question “What NSCs and for whom?” and consequently lead to the optimization of the grafting process and improvement of the clinical prognosis.