Cerebral infarcts, traumatic brain injury and spinal cord injury all share an ischemic basis, complicated by an acute inflammatory and edematous tissue response. Stroke in particular has been assessed by many groups as a potential target for cell replacement, and was among the first targets of stem and progenitor cell-based transplantation. (Hara et al., 2008; Nelson et al., 2002; Rosado-de-Castro et al., 2013). Yet stroke occurs in a fundamentally compromised environment of ischemic infarct, often in regions that have suffered chronic hypoxic ischemia, with its attendant gliosis and inflammation. In this challenging disease environment, essentially all cell types have been severely compromised, and their interactions distorted, with neurons often disconnected from their normal inputs and/or targets, and glial support disrupted. Any cell replacement strategy designed to repopulate areas of brain lost to ischemic injury would need to provide the multiplicity of neuronal phenotypes lost, to recapitulate their specific patterns of connection to one another, and in the cortex, to reproduce the laminar organization and connectivity of the host brain. Similarly, the glial populations would need to be replaced, while the
