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  • Title: Preconditioning of mesenchymal stem cells by sevoflurane to improve their therapeutic potential.
    Author: Sun X, Fang B, Zhao X, Zhang G, Ma H.
    Journal: PLoS One; 2014; 9(3):e90667. PubMed ID: 24599264.
    Abstract:
    BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) have been found to produce beneficial effects on ischemia-reperfusion injury. However, most of the MSCs died when transplanted into the ischemic tissue, which severely limit their therapeutic potential. METHODS: Using an in vitro model of hypoxia and serum deprivation (H/SD), we investigated the hypothesis that sevoflurane preconditioning could protect MSCs against H/SD-induced apoptosis and improve their migration, proliferation, and therapeutic potential. The H/SD of MSCs and neuron-like PC12 cells were incubated in a serum-free medium and an oxygen concentration below 0.1% for 24 h. Sevoflurane preconditioning was performed through a 2-h incubation of MSCs in an airtight chamber filled with 2 vol% sevoflurane. Apoptosis of MSCs or neuron-like PC12 cells was assessed using Annexin V-FITC/propidium iodide (PI). Furthermore, the mitochondrial membrane potential was assessed using lipophilic cationic probe. The proliferation rate was evaluated through cell cycle analysis. Finally, HIF-1α, HIF-2α, VEGF and p-Akt/Akt levels were measured by western blot. RESULTS: Sevoflurane preconditioning minimized the MSCs apoptosis and loss of mitochondrial membrane potential. Furthermore, it increased the migration and expression of HIF-1α, HIF-2α, VEGF, and p-Akt/Akt, reduced by H/SD. In addition, neuron-like PC12 cells were more resistant to H/SD-induced apoptosis when they were co-cultured with sevoflurane preconditioning MSCs. CONCLUSION: These findings suggest that sevoflurane preconditioning produces protective effects on survival and migration of MSCs against H/SD, as well as improving the therapeutic potential of MSCs. These beneficial effects might be mediated at least in part by upregulating HIF-1α, HIF-2α, VEGF, and p-Akt/Akt.
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