Another concern in regards to over-estimating therapeutic efficacy is in the use of xenografts to model cell therapy, and in particular assessing the performance of human cells in the mouse environment, diseased or otherwise. Human cells xenografted into the mouse brain retain species-specific and cell-autonomous attributes that distinguish them from their mouse hosts (Han et al., 2013; Oberheim et al., 2009). This is a specific issue in modeling the glial and myelin disorders, in which hGPCs may be used to model glial replacement-based therapeutic strategies. Yet human GPCs preferentially expand and migrate within murine hosts, out-competing resident mouse glial progenitors to ultimately dominate the glial population (Windrem et al., 2014). As a result, whether the therapeutic benefit afforded by hGPC engraftment of a myelin-deficient mouse model will prove as striking when human cells are transplanted into human hosts remains unclear. Mouse-to-mouse allografts have confirmed the ability of both healthy glial progenitors and neural stem cells to out-compete deficient glial progenitors and myelinate hypomyelinated hosts (Lachapelle et al., 1994; Mitome et al., 2001; Yandava et al., 1999), providing some assurance as
