Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain

Cell transplantation offers the potential to treat central nervous system injuries, largely because multiple mechanisms can be targeted in a sustained fashion. It is crucial that cells are transplanted into an environment that is favourable for extended survival and integration within the host tissue. Given the success of using fetal tissue grafts for traumatic brain injury, it may be beneficial to mimic key aspects of these grafts (e.g. three-dimensionality, cell-cell and cell-matrix support) to deliver cells. Extracellular matrix proteins such as fibronectin and laminin are involved in neural development and may provide adhesive support for donor cells and mediate subsequent cell signalling events. In this study, neural stem cells were transplanted into the traumatically injured mouse brain within a tissue-engineered construct containing either a laminin- or fibronectin-based scaffold. Cells delivered within the scaffolds were more widely distributed in the injured brain compared to cells delivered in media alone. There were no differences in donor cell survival at 1 week post-transplant; however, by 8 weeks post-transplant, cells delivered within the scaffolds showed improved survival compared to those transplanted in media alone. Survival was more enhanced with the laminin-based scaffold compared to the fibronectin-based scaffold. Furthermore, behavioural analyses indicated that mice receiving neural stem cells within the laminin-based scaffold performed significantly better than untreated mice on a spatial learning task, supporting the notion that functional recovery correlates positively with donor cell survival. Together these results suggest that the use of appropriate extracellular matrix-based scaffolds can be exploited to improve cell transplantation therapy.