Neural stem cell-mediated immunomodulation: repairing the haemorrhagic brain

Neural stem/precursor cells (NPCs) are broadly proposed as an alternative cell source to repair brain damage upon transplantation. NPC-driven brain repair has variably been shown in several pre-clinical models of neurological disorders. However, a comprehensive knowledge of the different mechanism(s) by which such cells exert their therapeutic potential is still lacking. While the replacement of lost or damaged cells was until a few years ago assumed to be the prime therapeutic mechanism of stem cells, it is now clear that transplanted somatic stem cells may simultaneously instruct several therapeutic mechanisms not confined to cell replacement on its own. Combining the overall therapeutic potential of NPCs in neurological disease, the concept of therapeutic plasticity has recently been proposed (Martino and Pluchino, 2006).The brain repair potential of transplanted stem cells in stroke-like conditions has solid pre-clinical evidence. It has been shown, with variable results, that NPCs—transplanted either systemically or intraparenchymally—display peculiar pathotropism toward specific sites of ischaemic damage, survive within the host for long periods of time, and establish a functional cross-talk with the different cell types of the (micro)environment. This NPC-dependent operational behaviour was first demonstrated to be capable of promoting CNS tissue recovery in mice with experimental bacterial collagenase-induced intracerebral haemorrage (ICH) (Jeong et al. , 2003) or acute middle cerebral artery occlusion-induced ischaemic stroke (Chu et al. , 2004). Interestingly, transplanted NPCs promoted significant functional …