Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells

The Management of Myelomeningocele Study demonstrated that in utero repair of myelomeningocele improved motor outcomes compared with postnatal repair. However, even after in utero repair, many children were still unable to walk. We have previously demonstrated that augmentation of in utero repair with early-gestation placental mesenchymal stromal cells (PMSCs) improves motor outcomes in lambs compared with standard in utero repair. The neuroprotective potential of PMSCs of all gestational ages has not been evaluated previously. PMSCs were isolated from discarded first trimester (n = 3), second trimester (n = 3), and term (n = 3) placentas by explant culture. Cytokine array analysis was performed. Secretion of two neurotrophic factors, brain-derived neurotrophic factor and hepatocyte growth factor, was evaluated by enzyme-linked immunosorbent assay. An in vitro neuroprotective assay demonstrated to be associated with in vivo function was performed. All cell lines secreted immunomodulatory and neuroprotective cytokines and secreted the neurotrophic factors evaluated. Increased neuroprotective capabilities relative to no PMSCs were demonstrated in two of the three first trimester cell lines (5.61, 4.96-6.85, P