Astrocytic and neuronal fate of mesenchymal stem cells expressing nestin

Classically, bone marrow mesenchymal stem cells (MSC) differentiate in vivo or in vitro into osteocytes, chondrocytes, fibroblasts and adipocytes. Recently, it was reported by several groups that MSC can also adopt a neural fate in appropriate in vivo or in vitro experimental conditions. However, it is unclear if those cells are really able to differentiate into functional neural cells and in particular into functional neurons. Some observations suggest that a cell fusion process underlies the neural fate adoption by MSC in vivo and first attempts to reproduce in vitro this neural fate decision in MSC cultures were unsuccessful. More recently, however, in several laboratories including ours, differentiation of MSC cultivated from adult rat bone marrow into astrocytes and neuron-like cells was demonstrated. More precisely, we stressed the importance of the expression by MSC of nestin, an intermediate filament protein associated with immaturity in the nervous system, as a pre-requisite to adopting an astrocytic or a neuronal fate in a co-culture paradigm. Using this approach, we have also demonstrated that the MSC-derived neuron-like cells exhibit several electrophysiological key properties classically devoted to neurons, including firing of action potentials. In this review, we will discuss the neurogenic potential of MSC, the factor(s) required for such plasticity, the molecular mechanism(s) underlying this neural plasticity, the importance of the environment of MSC to adopt this neural fate and the therapeutic potential of these observations.