Co-culture with bone marrow stromal cells protects PC12 neuronal cells from tumor necrosis factor-α-induced apoptosis by inhibiting the tumor necrosis factor receptor/caspase signaling pathway.

Bone marrow stromal cells (BMSCs), derived from the mesoderm, have been applied in the repair and reconstruction of injured tissues. The present study was conducted to explore the effects of BMSCs on cell viability of tumor necrosis factor-α (TNF-α)-stimulated PC12 cells. PC12 cells were co-cultured with BMSCs under TNF-α treatment, with normal PC12 cells as controls. Results from an MTT assay indicated that BMSCs significantly increased cell growth and proliferation of TNF-α-treated PC12 cells (survival rates were 56.71 and 76.86% for the positive control (PC) and co-culture group, respectively). Furthermore, Annexin V/propidium iodide staining and flow cytometric analysis demonstrated that TNF-α increased PC12-cell apoptosis from 3.49 to 40.74% in the negative control and PC group, and the apoptotic rate was significantly reduced upon co-culture with BMSCs to 16.97%. In addition, data from reverse transcription-quantitative polymerase chain reaction and western blot analyses illustrated that TNF-α-induced upregulation in TNF receptor (TNFR)-1 (TNFR1) and caspase-8 expression in PC12 cells were partially reversed by co-culture with BMSCs. In conclusion, the present study suggested that BMSCs protect PC12 cells against stimulation with TNF-α, which is partially mediated through the TNFR/caspase signaling pathway. The results of the present study also suggested a therapeutic use of BMSCs in clinical neurodegenerative diseases.

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