title: Pre-conditioned mesenchymal stem cells ameliorate renal ischemic injury in rats by augmented survival and engraftment.
abstract: BACKGROUND
  Ischemia is the major cause of acute kidney injury (AKI), associated with high mortality and morbidity. Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can be a potent therapeutic option for the cure of AKI.
  
  
  METHODS
  MSCs were cultured in four groups SNAP (S-nitroso N-acetyl penicillamine), SNAP + Methylene Blue (MB), MB and a control for in vitro analysis. Cultured MSCs were pre-conditioned with either SNAP (100 μM) or MB (1 μM) or both for 6 hours. Renal ischemia was induced in four groups (as in in vitro study) of rats by clamping the left renal padicle for 45 minutes and then different pre-conditioned stem cells were transplanted.
  
  
  RESULTS
  We report that pre-conditioning of MSCs with SNAP enhances their proliferation, survival and engraftment in ischemic kidney. Rat MSCs pre-conditioned with SNAP decreased cell apoptosis and increased proliferation and cytoprotective genes' expression in vitro. Our in vivo data showed enhanced survival and engraftment, proliferation, reduction in fibrosis, significant improvement in renal function and higher expression of pro-survival and pro-angiogenic factors in ischemic renal tissue in SNAP pre-conditioned group of animals. Cytoprotective effects of SNAP pre-conditioning were abrogated by MB, an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase.
  
  
  CONCLUSIONS
  The results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury.
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. masoudshareef@gmail.com
authors.forename: Muhammad Shareef
authors.initials: MS
authors.lastname: Masoud
authors.forename: Sanam Saiqa
authors.initials: SS
authors.lastname: Anwar
authors.forename: Muhammad Zeeshan
authors.initials: MZ
authors.lastname: Afzal
authors.forename: Azra
authors.initials: A
authors.lastname: Mehmood
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000628:therapy*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
chemical_list: D003470:Culture Media; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine