The vascular stem cell niche: roadmap for transplanted neural progenitor cells during environmental enrichment?

Abstract

One of the challenges of cell transplantation into the brain is poor graft survival. Graft survival may be affected by an immunological response of the host towards transplanted cells, shear injury to cells during transplantation or an unsuitable micro-environment for the transplanted cell type. Neural progenitor cells have an affinity to laminin, which is commonly used to maintain neural progenitors as monolayer cultures in vitro. The affinity of neural progenitor cells to laminin is based on the high expression of α6β1 integrin, which is required for binding of neural progenitors to endothelial cells (Hall et al., 2006; Shen et al., 2008). Mice with targeted disruption of β1 integrin have substantial layering deficits in developing neocortex (Loulier et al., 2009). Laminin is an important constituent of the basal membrane of brain capillaries. We also found abundant expression of laminin in the basal cistern along the apical surface of the molecular layer of the dentate gyrus (Jamal et al., 2015). Transplanted dentate progenitor cells did not survive in the transplant core within the dentate gyrus, but initially rather exclusively survived along the laminin scaffold of the basal cistern (Figure 1A). The laminin of the basal cistern is connected to the laminin of the capillary network of the dentate gyrus. It appeared as if transplanted dentate progenitor cells initially settled on the dense laminin scaffold of the basal cistern and then migrated into the hippocampal formation using laminin of dentate capillaries as tram tracks (Figure ​Figure1B1B, ​,C).C). Even though we expanded neural progenitor cells on laminin-coated tissue culture flasks, which may have selected for neural progenitor cells with a strong affinity to laminin, we observed the same in vivo affinity to laminin after growing neural progenitor cells as neurospheres for 5 days before transplantation. Also, previous experiments with neural progenitor cells grown exclusively as neurospheres before transplantation showed the greatest survival of cells along the laminin-rich basal cistern adjacent to the dentate gyrus instead of in the transplant core within the parenchyma of the hippocampal formation (Waldau et al., 2010).