title: Preconditioning of mesenchymal stem cells by sevoflurane to improve their therapeutic potential.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005434:Flow Cytometry; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008738:Methyl Ethers / Q000494:pharmacology*; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D015415:Biomarkers; D016895:Culture Media, Serum-Free; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008738:Methyl Ethers; D000077149:Sevoflurane; D051057:Proto-Oncogene Proteins c-akt