Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC). Cells were treated with: (1) TPA, forskolin, IBMX, FGF-1 or (2) retinoic acid and 2-mercaptoethanol (BME). Treatment (1) induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1) compared with treatment (2). In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments.Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.Up until only a few years ago, the fate of adult stem cells was believed to be limited to their tissue of origin. However, it has recently been demonstrated that in several tissues adult stem cells may undergo a fate other than that habitually manifested in physiological conditions. As an example, stem cells isolated from bone marrow can differentiate not only into blood cells, but also into hepatocytes [1], skeletal muscle [2] and cardiomyocytes [3]. Even more surprisingly, recent studies have shown that stem cells in vivo may even give rise to neural cells, thus representing an important alternative to embryonic cells for therapeutic transplantation [4,5]. Indeed, the original idea of substituting neurons damaged by different pathological events with undamaged heterologous neurons has not so far afforded satisfactory results [6,7]. On the other hand, although the discovery of the existence of neural stem cells in the adult human brain [for a review see [8]] is certainly a milestone in the field, it is difficult to conceive a method leading to manipulation and reimplantation of neural stem cells taken directly from the patient