title: Original article anti-oxidant pathways are stimulated by mesenchymal stromal cells in renal repair after ischemic injury.
abstract: OBJECTIVE
  Ischemia-reperfusion (IR) injury is a common cause of acute renal failure. Bone marrow (BM)-derived mesenchymal stromal cells (MSC) delivered after renal IR are renoprotective, but knowledge of the protective mechanism is still in development. This investigation analyzed the protective molecular mechanisms of MSC, in particular relating to modulated oxidative stress.
  
  
  METHODS
  In vivo and in vitro models of renal IR were analyzed with and without MSC. In vivo, adult male Sprague-Dawley rats were subjected to 40-min unilateral renal IR. Rat BM-derived MSC were administered at 24 h post-IR (IR + MSC). Other groups had IR but no MSC, or MSC but no ischemia (all groups n = 4). Apoptosis, inflammation, oxidative stress and reparative signal transduction molecules or growth factors were studied 4 days post-IR. In vitro, protection by MSC against oxidative stress (0.4 mm hydrogen peroxide) was investigated using rat renal tubular epithelial cells (NRK52E) with or without MSC in co-culture (tissue culture trans-well inserts), followed by similar analyses to the in vivo investigation.
  
  
  RESULTS
  In vivo, kidneys of IR + MSC animals had significantly increased cell proliferation/regeneration (cells positive for proliferating cell nuclear antigen, expression of epidermal growth factor), increased heme-oxygenase-1 (improved cell survival, anti-oxidant) and decreased 8-OHdG (decreased oxidative stress). In vitro, MSC delivered with oxidative stress significantly decreased apoptosis and Bax (pro-apoptotic protein), and increased mitosis and phospho-ERK1/2, thereby minimizing the damaging outcome and maximizing the regenerative effect after oxidative stress.
  
  
  CONCLUSIONS
  The benefits of MSC, in IR, were primarily pro-regenerative, sometimes anti-apoptotic, and novel anti-oxidant mechanisms were identified.
authors.affiliation: Centre for Kidney Disease Research, University of Queensland School of Medicine, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: McTaggart
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.forename: Glenda C
authors.initials: GC
authors.lastname: Gobe
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D002460:Cell Line; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000235:genetics; D015427:Reperfusion Injury / Q000473:pathology* / Q000628:therapy; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D051028:bcl-2-Associated X Protein; D004815:Epidermal Growth Factor; D051547:Heme Oxygenase-1