title: Lipopolysaccharide preconditioning of adipose-derived stem cells improves liver-regenerating activity of the secretome.
abstract: BACKGROUND
  Growing recognition of paracrine mechanisms in stem cell plasticity has resulted in considerable interest in stem cell-derived secretome. The aim of this study was to investigate the effects of lipopolysaccharide (LPS) preconditioning on the composition and hepatic regenerative activity of adipose-derived stem cell (ASC) secretome.
  
  
  METHODS
  Conditioned medium (CM) and LPS-CM were obtained after culturing human ASCs without or with low-dose LPS (0.5 ng/mL) for 24 hours. Untreated and thioacetamide-treated mouse AML12 hepatocytes were incubated for 24 hours with the control medium, LPS (0.5 ng/mL), CM, and LPS-CM and then cell viabilities were compared. CM and LPS-CM were also intravenously administered to partially hepatectomized mice, and their effects on liver regeneration were assessed by using liver weight measurements, immunohistochemistry, and Western blotting.
  
  
  RESULTS
  In the in vitro experiments, LPS preconditioning of ASCs enhanced the mRNA expression levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor, and vascular endothelial growth factor, which evoke inflammatory response or liver regeneration. LPS-CM significantly promoted thioacetamide-damaged AML12 cell viability compared with CM-incubated cells and the control cells (77%, 69%, and 65% P<0.05). In the in vivo experiment, LPS-CM infusion into the partially hepatectomized mice significantly reduced serum IL-6 and TNF-α levels compared with the other groups (P<0.05) on days 1 and 2 after partial hepatectomy. Moreover, LPS-CM infusion enhanced liver regeneration (based on the liver weight changes at day 7 after partial hepatectomy, 3.73% versus 3.22% in the CM group; P<0.05) and significantly reduced the elevated serum levels of aspartate transaminase and alanine transaminase (at day 1, P<0.05).
  
  
  CONCLUSIONS
  Our results suggest that LPS preconditioning effectively stimulates ASCs to produce the secretome beneficial to hepatic regeneration. Thus, optimizing ASC secretome profile by LPS preconditioning could be a promising approach to treat liver diseases by using stem cells.
authors.affiliation: Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daeheung-dong 520-2, Joong-gu, Daejeon, Republic of Korea. zambo9@catholic.ac.kr.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daeheung-dong 520-2, Joong-gu, Daejeon, Republic of Korea. redfox0024@nate.com.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daeheung-dong 520-2, Joong-gu, Daejeon, Republic of Korea. luislee@catholic.ac.kr.
authors.forename: Sang Kuon
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daeheung-dong 520-2, Joong-gu, Daejeon, Republic of Korea. sejoonkim@hanmail.net.
authors.forename: Say-June
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013853:Thioacetamide / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013853:Thioacetamide