Recent Advances in Neuronal-like Differentiation of Mesenchymal Stem/Stromal Cells

Mesenchymal stem/stromal cells (MSCs) have been widely investigated in recent decades because of their multipotent differentiation abilities. In fact, MSCs are able to differentiate not only into mesodermal cell lines (adipocytes, chondrocytes, osteocytes), but also into neuronal and glial cells. MSCs can be derived from different sources, such as bone marrow, adipose tissue, peripheral blood and various neonatal birth-associated tissues. They are suitable candidate in cell-based approaches for both autologous and heterologous transplantation in the field of regenerative medicine. Unlike other types of stem cells, MSCs raise no ethical issues and feature low risks of tumorigenesis after transplantation into humans or animals. In addition, they may exert beneficial effects due to their paracrine actions which help tissue recovery. Numerous studies describe effects obtained following MSC treatments in a variety of human pathologies, including nervous system diseases. The nervous tissue is characterized by very limited recovery properties, likely because of a scarce presence of stem cell niches, which are confined to the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. These niches cannot be able to counteract the neuronal loss after damage or degenerative events. Many efforts have been made to obtain functional neuronal differentiated MSCs to be used for transplantation. However, evidence of complete neuronal maturation and functional integration of neuronal-like MSCs remains limited, and clinical studies have used undifferentiated MSCs rather than neuronal-like cell populations. In this review, we mainly focus on various differentiation protocols that have been adopted for in vitro studies, taking also into account the underlying pathways involved.