Therapeutic stem cell plasticity orchestrates tissue plasticity

In ischaemic stroke, recanalizing and neuroprotective therapeutic strategies have failed, so far, adequately to prevent or reverse tissue damage. The sudden and unpredictable onset (Roger et al ., 2011) and the local tissue complexity (Lo, 2008) are the main limiting factors. Nevertheless, tissue damage and loss of function can—for a definite period after stroke—be constrained by a ‘plastic’ reaction that the brain is capable of setting in place, which acts to reconstruct neuronal circuits.The fundamental premise of the idea of brain plasticity in stroke was inferred by Paul Broca (1824–80) in 1865. While studying autoptic cases of aphasic patients, he hypothesized that a lost cortical function (namely speech) can be sustained by another brain area, even localized in the contralateral hemisphere (Broca, 1865). Since then, many scientists have investigated, at both macroscopic and microscopic levels, the mechanisms underlying CNS remodelling after injury and, nowadays, there is no uncertainty that the nervous tissue is endowed with a very considerable degree of plasticity (Payne and Lomber, 2001). The rapid and massive structural changes occurring at synaptic (e.g. strength of connectivity, synaptogenesis), dendritic and axonal levels (e.g. sprouting, branching), during both physiological and pathological conditions, are the most striking examples of this phenomenon.In recent years, the possibility that the nervous system can also achieve change in structures that alter networks of functional connectivity (Paillard, 1976) has been reinforced by the discovery of another adaptive mechanism termed neurogenesis (Altman and Das, 1965). The adult CNS naturally replaces extruded or worn out cells through generation of new elements of neuronal and glial lineages from neural stem and progenitor cells. The discovery of adult neuro(glio)genesis has fostered the development of therapies based on neural progenitor cell transplantation for acute and chronic neurodegenerative disorders, including stroke (Lindvall and Kokaia, 2010). However, it is still not …