While the development of specified neural and glial cell types from hESCs and hiPSCs has been met with great enthusiasm in the stem cell community, the rush towards their clinical use must be tempered by a number of issues that remain problematic in the transition from bench-to-bedside. Issues of potential tumorigenicity, immunogenicity, heterotopic differentiation, and adventitious viral introduction have been extensively discussed in recent reviews (Kaneko and Yamanaka, 2013; Yu et al., 2013). In particular, teratoma formation from residual pluripotential cells is a well-known risk that has been mitigated by the differentiation of cells in vitro towards terminal lineages, combined with cell sorting technologies to enrich lineage-restricted progenitors and remove persistent PSCs. However, the potential for tissue-specific tumor formation, with oncogenesis from partially-differentiated hES and hiPS cells, may be an even greater concern, that is not alleviated by the absence of pluripotent cells from grafts. Neuroepithelial tumors have been found in grafts of hESC-derived neural stem cells and their derived neuronal progenitors (Roy et al., 2006), as well as in grafts of cultured NSCs expanded for prolonged periods under constant
