In Vitro Maturation of Human iPSC-Derived Neuroepithelial Cells Influences Transplant Survival in the Stroke-Injured Rat Brain

Stem cell transplantation is a promising strategy for brain tissue regeneration; yet, despite some success, cell survival following transplantation remains low. In this study, we demonstrate that cell viability is enhanced by control over maturation of neuronal precursor cells, which are delivered in an injectable blend of hyaluronan and methylcellulose. We selected three subpopulations of human neuronal precursor cells derived from a cortically specified neuroepithelial stem cell (cNESC) population based on differences in expression of multipotent and neuron-specific proteins: early-, mid-, and late-differentiated neurons. These cells were transplanted into an endothelin-1 stroke-injured rat brain and their survival and fate were investigated 1 week later. Significantly, more cells were found in the brain after transplanting early- or mid- differentiated cNESCs compared to the late-differentiated population. The mid-differentiated population also had significantly more -III tubulin-positive cells than either the early- or late-differentiated populations. These results suggest that maturity has a significant impact on cell survival following transplantation and cells with an intermediate maturity differentiate to neurons.