A recurrent theme in the design of clinically-meaningful cell therapeutic strategies is ensuring the proper pairing of disease targets with the right donor phenotypes, i.e., those able to achieve functionally-effective cell replacement and circuit repair in the disease environment. Yet a number of recent efforts have promulgated the use of donor cells that may be ill-suited for the disease targets to which they have been applied. Mesenchymal stem or stromal cells are a case in point. The homogeneity and ease of production of these cells has led to substantial interest in their deployment as cellular therapeutics, and their anti-inflammatory properties have led to their assessment in a broad variety of disease models and clinical targets alike (Einstein and Ben-Hur, 2008; Fainstein et al., 2008). Yet grafted MSCs typically do not survive in the adult human CNS, and early reports of their ability to produce mature neural phenotypes have been largely discredited. As such, the use of MSCs would seem logically limited to short-term immune modulation in settings for which pharmacological immune suppression has been found ineffective or otherwise ill-advised, such
