title: Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion.
abstract: BACKGROUND
  Acute coronary syndrome leads to systemic responses, including activation of the sympathetic nervous system, inflammation of atherosclerotic lesions, changes in metabolism and gene expressions of remote organs such as the spleen, bone marrow, and liver. Clinical trials and experimental studies have demonstrated that therapy with adipose-derived regenerative cells (ADRCs) attenuates myocardial ischemia/reperfusion (I/R) injury. The aim of this study is to investigate the role of ADRCs in regulating systemic reactions following I/R.
  
  
  METHODS
  Isolated ADRCs were obtained from green fluorescent protein transgenic male mice. Flow cytometry revealed that freshly isolated ADRCs expressed stem cell markers CD90 and Sca-1, and mesenchymal lineage marker. These cells exhibited multilineage differentiation into adipogenic, osteogenic, and chondrogenic lineages. Wild-type mice were subjected to 30 min of left ascending coronary ischemia and 24 h reperfusion. Freshly isolated ADRCs (105 cells) or vehicle (VEH), were administered intravenously through the tail at the time of reperfusion.
  
  
  RESULTS
  Compared to VEH, administration of ADRCs significantly reduced circulating troponin levels 24 h after I/R. Using quantitative real-time polymerase chain reaction analysis, the present study confirms that I/R-induced increase of factor X mRNA expression in the liver and was significantly inhibited by ADRCs compared to VEH. Administration of ADRCs significantly reduced the I/R-induced increase in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-18 seen in mice receiving VEH.
  
  
  CONCLUSIONS
  These results suggest that administration of ADRCs could have an important role in reducing myocardial injury and regulating the hepatic gene expression profile following I/R.
authors: Masayuki
authors: M
authors: Takamura
authors: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan. usuiso@m-kanazawa.jp.
authors: Soichiro
authors: S
authors: Usui
authors: Oto
authors: O
authors: Inoue
authors: Hiroshi
authors: H
authors: Ootsuji
authors: Shin-Ichiro
authors: SI
authors: Takashima
authors: Ayano
authors: A
authors: Nomura
authors: Takeshi
authors: T
authors: Kato
authors: Hisayoshi
authors: H
authors: Murai
authors: Hiroshi
authors: H
authors: Furusho
authors: Yoshio
authors: Y
authors: Sakai
authors: Shuichi
authors: S
authors: Kaneko
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005170:Factor X / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000473:pathology*
chemical_list: D016207:Cytokines; D005170:Factor X
keywords: adipose-derived regenerative cells; cytokine; factor X; liver; myocardial ischemia/reperfusion