title: Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats.
abstract: We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina.
  
  
  
  Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays.
  
  
  
  Eyes injected with hypoxic BMSC-conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium.
  
  
  
  The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect.
authors.affiliation: Department of Anesthesiology, University of Illinois, Illinois, United States 3Department of Anesthesia and Critical Care, University of Chicago, Illinois, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Roth
authors.affiliation: Department of Anesthesia and Critical Care, University of Chicago, Illinois, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Dreixler
authors.affiliation: Department of Anesthesiology, University of Illinois, Illinois, United States.
authors.forename: Biji
authors.initials: B
authors.lastname: Mathew
authors.affiliation: Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States 5Surgery, University of Chicago Medicine, University of Chicago, Illinois, United States.
authors.forename: Irina
authors.initials: I
authors.lastname: Balyasnikova
authors.affiliation: Department of Anesthesia and Critical Care, University of Chicago, Illinois, United States.
authors.forename: Jacob R
authors.initials: JR
authors.lastname: Mann
authors.affiliation: Department of Anesthesia and Critical Care, University of Chicago, Illinois, United States.
authors.forename: Venkat
authors.initials: V
authors.lastname: Boddapati
authors.affiliation: Surgery, University of Chicago Medicine, University of Chicago, Illinois, United States.
authors.forename: Lai
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States 5Surgery, University of Chicago Medicine, University of Chicago, Illinois, United States.
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004195:Disease Models, Animal; D004596:Electroretinography; D000860:Hypoxia / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D056965:Injections, Intraocular; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D019194:Ischemic Preconditioning; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology* / Q000503:physiopathology; D012164:Retinal Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D012165:Retinal Ganglion Cells / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned