title: Human cord blood CD133+ cells exacerbate ischemic acute kidney injury in mice.
abstract: BACKGROUND
  Acute kidney injury (AKI) in humans has few therapeutic options. In experimental models, administration of progenitor cells facilitates recovery from AKI. Human umbilical cord-derived CD133(+) progenitor cells promote endothelial repair in ischemic limb, heart and brain tissue.
  
  
  METHODS
  We examined the effects of human CD133(+) progenitor cells in bilateral ischemia-reperfusion (I/R) kidney injury in non-obese diabetic severe combined immunodeficient mice. CD133(+) cells from human cord blood were injected intravenously at the time of reperfusion and the extent of injury was determined by plasma biochemistry and kidney histology.
  
  
  RESULTS
  In mice with I/R, fluorescently labeled CD133(+) cells were detected in blood 2 min after injection but decreased rapidly thereafter with no evidence of homing to the kidneys. In mice subjected to I/R, CD133(+) cells significantly increased plasma urea and Cr at 24 h compared to vehicle- or CD133(-) cell-treated mice. CD133(+) cells exacerbated tubular necrosis and apoptosis, increased plasma tumor necrosis factor-α and increased kidney neutrophil infiltration. In contrast, CD133(+) cells did not affect tubular cell proliferation. Administration of CD133(+) cells to FVB/N mice post-I/R also augmented kidney injury.
  
  
  CONCLUSIONS
  These data indicate that human cord blood-derived CD133(+) cells unexpectedly exacerbate ischemic AKI in mice, possibly through soluble factors. Our study highlights the importance of caution in cell-based therapies for human AKI.
authors.affiliation: Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
authors.forename: Dylan
authors.initials: D
authors.lastname: Burger
authors.forename: Alex
authors.initials: A
authors.lastname: Gutsol
authors.forename: Anthony
authors.initials: A
authors.lastname: Carter
authors.forename: David S
authors.initials: DS
authors.lastname: Allan
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burns
mesh_terms: D000071916:AC133 Antigen; D058186:Acute Kidney Injury / Q000473:pathology / Q000628:therapy*; D000818:Animals; D015703:Antigens, CD / Q000097:blood; D017209:Apoptosis; D049109:Cell Proliferation; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009504:Neutrophils / Q000473:pathology; D010455:Peptides / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D009195:Peroxidase