Mesenchymal stem cell transplantation has been proposed as a promising therapy for regeneration of damaged tissues-especially, bone marrow mesenchymal stem cell (BMSC) transplantation therapy is considered to be an effective strategy for treating various injures in recent years. However, poor viability of transplanted BMSCs in injured tissues has limited their therapeutic efficiency. Nerve growth factor (NGF) has been reported to be a pro-survival factor in series of cells. Moreover, NGF could improve BMSC viability and activate anti-apoptotic pathway. Therefore, we are interested to know whether NGF promoted BMSC survival in transplanted tissue. In this study, we investigated the protective effect and potential mechanisms of NGF against apoptosis of BMSCs in vitro. 2,5-hexanedione (HD) was the apoptosis inducer. BMSCs were treated with 40 mM HD and different concentrations of NGF (0, 50, 100, 200 μg/L) together for 24 h. Results showed that NGF treatment increased the viability of BMSCs exposed to HD. Moreover, NGF effectively suppressed HD-induced apoptosis which was characterized by inhibiting caspase-3 activity, as well as mitochondrial transmembrane potential depolarization. Mechanistically, it was found that NGF promoted phosphorylation of Akt and Bad, which is TrkA dependent. However, K252a and MK-2206 (TrkA and Akt inhibitor, respectively) suppressed the anti-apoptosis of NGF, indicating the protective effect of NGF on BMSCs apoptosis via a novel Akt/Bad pathway. The findings suggested that NGF may be used as an effective protective agent against BMSC apoptosis so as to promote the survival rate of transplanted BMSCs and their tissue repair capability.
Keywords: Akt/Bad pathway; Apoptosis; Mesenchymal stem cells; NGF.