Promoting neural transdifferentiation of BMSCs via applying synergetic multiple factors for nerve regeneration

The strategy of using multipotential stem cells like bone mesenchymal stromal cells (BMSCs) for nerve tissue engineering is proven feasible. The promotion effects on neural transdifferentiation of BMSCs from factors including nerve growth factor (NGF), laminin and electrical stimulation (ES) have been reported, while it is not known if these factors can achieve a strong synergetic impact when the cells are cultured on conductive substrates. In this study, it was identified that any single factor (NGF, laminin, or conductive substrate) combined with ES demonstrated the capacity to induce BMSCs transdifferentiating into neural cells, while the efficiency was found in the order of NGF > laminin > conductive substrate. The combination of any two of the factors would be more efficient in inducing the neural transdifferentiation than individual factor. As expected, the strongest promotion in inducing BMSCs to transdifferentiate into neural cells was identified when BMSCs were cultured on laminin-treated conductive nanofibrous mesh in the presence of NGF and under proper ES simultaneously, showing significant synergetic efficiency from these multiple factors. Studies on the Notch-1 signaling pathway, a main negative regulator of neurogenesis, revealed these factors sharing a similar molecular mechanism in regulating the neural transdifferentiation of BMSCs. The results suggested that satisfactory nerve regeneration might be achievable if these synergetic multiple factors could be involved in nerve guidance conduit design, especially, when BMSCs were applied as co-implanted cells.