title: Elimination of reperfusion-induced microcirculatory alterations in vivo by adipose-derived stem cell supernatant without adipose-derived stem cells.
abstract: BACKGROUND
  In the present study, the authors hypothesized that adipose-derived stem cells in cell culture may secrete multiple cytokines in the supernatant, which might have a significant impact in vivo on the reperfusion-induced microcirculatory alterations and endothelial dysfunction.
  
  
  METHODS
  Fat tissue was surgically harvested from rat flanks and processed for adipose-derived stem cell isolation; cells (1 × 10(6)) were subcultured for 3, 6, 9, and 12 days without passage. The postcultivated medium was harvested with medium change every 3 days. After centrifugation, the supernatant was collected and stored at -20°C. Supernatant collected on day 9 was analyzed for eight oxidative stress cytokines by an enzyme-linked immunosorbent assay strip. The effect of the supernatant on the reperfusion-induced microcirculatory alterations was examined in the vascular pedicle of isolated rat cremaster muscles subjected to 4 hours of ischemia followed by 2 hours of reperfusion.
  
  
  RESULTS
  Enzyme-linked immunosorbent assay results demonstrated that adipose-derived stem cells produced several highly expressed cytokines in the supernatant. The average concentration of interleukin-6, in particular, was 5-fold higher compared with control. The reperfusion-induced vasospasm, arteriole stagnation, and the capillary no-reflow that often appear in the early phase of reperfusion were eliminated by adipose-derived stem cell supernatant.
  
  
  CONCLUSIONS
  Adipose-derived stem cells in cell culture display cytokine secretory properties that enable the cells to act through paracrine signaling. The supernatant even without cells could be used as a paracrine agent to interfere with the reperfusion-induced microcirculatory alterations and endothelial dysfunction.
authors: Las Vegas, Nev. From the Division of Plastic Surgery, University of Nevada School of Medicine.
authors: Wei Z
authors: WZ
authors: Wang
authors: Xin-Hua
authors: XH
authors: Fang
authors: Shelley J
authors: SJ
authors: Williams
authors: Linda L
authors: LL
authors: Stephenson
authors: Richard C
authors: RC
authors: Baynosa
authors: Kayvan T
authors: KT
authors: Khiabani
authors: William A
authors: WA
authors: Zamboni
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D016207:Cytokines